Evaluating a Service-Oriented Architecture

DTIC Science & Technology

2007-09-01

See the description on page 13. SaaS Software as a service ( SaaS ) is a software delivery model where customers don’t own a copy of the application... serviceability REST Representational State Transfer RIA rich internet application RPC remote procedure call SaaS software as a service SAML Security...Evaluating a Service -Oriented Architecture Phil Bianco, Software Engineering Institute Rick Kotermanski, Summa Technologies Paulo Merson

A computational model for simulating text comprehension.

PubMed

Lemaire, Benoît; Denhière, Guy; Bellissens, Cédrick; Jhean-Larose, Sandra

2006-11-01

In the present article, we outline the architecture of a computer program for simulating the process by which humans comprehend texts. The program is based on psycholinguistic theories about human memory and text comprehension processes, such as the construction-integration model (Kintsch, 1998), the latent semantic analysis theory of knowledge representation (Landauer & Dumais, 1997), and the predication algorithms (Kintsch, 2001; Lemaire & Bianco, 2003), and it is intended to help psycholinguists investigate the way humans comprehend texts.

The Role of Heparin-Binding EGF-Like Growth Factor in Breast Cancer

DTIC Science & Technology

1996-10-01

MgCl2 and proteinae inhibitors: leupeptin (5 p.g/ml), aprotinin (20 gg/ml) and phenylmethylsulfonyl fluoride (35.8 gtg/ml) and incubated for 15 min at 40C...Normanno, N., Merlo, G., Salomon, D.S., and Callahan, R.: Absence of p53 mutations in nontransformed human mammary epithelial cell lines. Life Sci. Adv...Tortora, G., Basolo, F., Fiore, L., Fontanini, G., Merlo, G., Salomon, D.S., Bianco, A.R., and Ciardiello, F.: Effects of mutant p53 genes on transformation

Teachers Explore Earth Science in South America

NASA Astrophysics Data System (ADS)

Passow, Michael; Krusche, Nisia; Carneiro, Celso D. R.

2010-11-01

Rain, Rocks, and Climate: A Geophysical Information for Teachers Workshop; Foz do Iguaçu, Brazil, 8-9 August 2010; Classroom teachers and university professors from two continents joined to learn about “rocks, rain, and climate” in the Geophysical Information for Teachers (GIFT) workshop at the AGU Meeting of the Americas held in Brazil. This was the first GIFT workshop in South America. GIFT workshops have long been part of AGU Fall Meetings in San Francisco, European Geosciences Union Spring Meetings in Vienna, and other AGU conferences. Two Brazilian geoscience professors, Celso Dal Ré Carneiro of State University of Campinas and Nisia Krusche of Federal University of Rio Grande, organized the program, together with a high-school teacher from the United States, Michael J. Passow of Dwight Morrow High School, Englewood, N. J. Joining the presenters were 15 Brazilian teachers and another teacher from New Jersey.

Social inequalities in the face of scientific and technological development: an antinomy or an historic problem?

PubMed

Delgado, Guilherme Costa

2017-07-01

This paper aims to conduct a conceptual analysis of the relationship between scientific and technical progress and social equality, or the reduction of inequalities. We examine this relationship by drawing on three theoretical perspectives: 1) ethical economics, championed by classical economic thinkers and centered on utilitarian self-interest, 2) Mainstream theories of economic development espousing the endogenous link between labor productivity growth and technical progress, 3) the critique of theories of economic development that emerged in the second half of the twentieth century, including Celso Furtado's critique of the theory of underdevelopment, emphasizing the prevalence of egalitarian tendencies, and ecological economics, which suggest alternative paths to those set by "classical" theories of development. The fundamental antinomy posed by the title of this article, characterized by an intrinsic contradiction between technical progress and social equality, strictly presupposes the ethical economics perspective, dominated by the social relations that constitute the "social order".

Characterization of a grape class IV chitinase.

PubMed

Vincenzi, Simone; Bierma, Jan; Wickramasekara, Samanthi I; Curioni, Andrea; Gazzola, Diana; Bakalinsky, Alan T

2014-06-18

A chitinase was purified from Vitis vinifera Manzoni Bianco grape juice and characterized. On the basis of proteomic analysis of tryptic peptides, a significant match identified the enzyme as a type IV grape chitinase previously found in juices of other V. vinifera varieties. The optimal pH and temperature for activity toward colloidal chitin were found to be 6 and 30 °C, respectively. The enzyme was found to hydrolyze chitin and oligomers of N-acetylglucosamine, generating N,N'-diacetylchitobiose and N-acetylglucosamine as products, but was inactive toward N,N'-diacetylchitobiose. The enzyme exhibited both endo- and exochitinase activities. Because yeast contains a small amount of chitin in the cell wall, the possibility of growth inhibition was tested. At a concentration and pH expected in ripe grapes, no inhibition of wine yeast growth by the chitinase was observed.

Characterization of a Grape Class IV Chitinase

PubMed Central

2015-01-01

A chitinase was purified from Vitis vinifera Manzoni Bianco grape juice and characterized. On the basis of proteomic analysis of tryptic peptides, a significant match identified the enzyme as a type IV grape chitinase previously found in juices of other V. vinifera varieties. The optimal pH and temperature for activity toward colloidal chitin were found to be 6 and 30 °C, respectively. The enzyme was found to hydrolyze chitin and oligomers of N-acetylglucosamine, generating N,N′-diacetylchitobiose and N-acetylglucosamine as products, but was inactive toward N,N′-diacetylchitobiose. The enzyme exhibited both endo- and exochitinase activities. Because yeast contains a small amount of chitin in the cell wall, the possibility of growth inhibition was tested. At a concentration and pH expected in ripe grapes, no inhibition of wine yeast growth by the chitinase was observed. PMID:24845689

European National Society Cardiovascular Journals

PubMed Central

Alfonso, F.; Ambrosio, G.; Pinto, F.J.; van der Wall, E.E.

2008-01-01

Anesti Kondili MD, Djamaleddine Nibouche MD, Karlen Adamyan MD, Kurt Huber MD, Hugo Ector MD, Izet Masic MD, Rumiana Tarnovska MD, Mario Ivanusa MD, Vladimír Stane˘k MD, Jørgen Videbæk MD, Mohamed Hamed MD, Alexandras Laucevicius MD, Pirjo Mustonen MD, Jean-Yves Artigou MD, Ariel Cohen MD, Mamanti Rogava MD, Michael Böhm MD, Eckart Fleck MD, Gerd Heusch MD, Rainer Klawki MD, Panos Vardas MD, Christodoulos Stefanadis MD, József Tenczer MD, Massimo Chiariello MD, Aleksandras Laucevicius MD, Joseph Elias MD, Halima Benjelloun MD, Olaf Rødevand MD, Piotr Kul/akowski MD, Edvard Apetrei MD, Victor A. Lusov MD, Rafael G. Oganov MD, Velibor Obradovic MD, Gabriel Kamensky MD, Miran F. Kenda MD, Christer Höglund MD, Thomas F. Lüscher MD, René Lerch MD, Moufid Jokhadar MD, Habib Haouala MD, Vedat Sansoy MD, Valentin Shumakov MD, Adam Timmis MD. (European National Society Cardiovascular Journals Editors, see Appendix for complete affiliations) PMID:18665206

The Effect of Underwater Imagery Radiometry on 3d Reconstruction and Orthoimagery

NASA Astrophysics Data System (ADS)

Agrafiotis, P.; Drakonakis, G. I.; Georgopoulos, A.; Skarlatos, D.

2017-02-01

The work presented in this paper investigates the effect of the radiometry of the underwater imagery on automating the 3D reconstruction and the produced orthoimagery. Main aim is to investigate whether pre-processing of the underwater imagery improves the 3D reconstruction using automated SfM - MVS software or not. Since the processing of images either separately or in batch is a time-consuming procedure, it is critical to determine the necessity of implementing colour correction and enhancement before the SfM - MVS procedure or directly to the final orthoimage when the orthoimagery is the deliverable. Two different test sites were used to capture imagery ensuring different environmental conditions, depth and complexity. Three different image correction methods are applied: A very simple automated method using Adobe Photoshop, a developed colour correction algorithm using the CLAHE (Zuiderveld, 1994) method and an implementation of the algorithm described in Bianco et al., (2015). The produced point clouds using the initial and the corrected imagery are then being compared and evaluated.

The Rise and Development of Physics in Cuba: An Interview with Hugo Pérez Rojas in May 2009

NASA Astrophysics Data System (ADS)

Baracca, Angelo

Hugo Celso Pérez Rojas was born in 1938, and works as a senior researcher at the Institute of Cybernetics, Mathematics and Physics, at the Ministry of Science and Technology, Cuba. Pérez Rojas is emeritus member of the Academy of Sciences of Cuba, member of the Latin American Academy of Sciences and Fellow TWAS since 1994. He was one of the founders of the School of Physics in the University of Havana in 1962, and moved in 1971 to the Cuban Academy of Sciences. His national awards include the Rafael Maria Mendive and Carlos J. Finlay Medals. He was awarded in 2011 the National Prize in Physics from the Cuban Physical Society. His interests include quantum field theory and its applications to finite temperature problems in high-energy physics and condensed matter. Among these, Pérez Rojas has devoted special attention to quantum electrodynamics in matter and in vacuum in the presence of external fields, phase transitions in electroweak theory, relativistic quantum Hall effect, Bose-Einstein condensation in magnetic fields, and applications of physics to social sciences. He is interviewed here by Angelo Baracca in May 2009.

Tephra and cryptotephra in a 60,000-year-old lacustrine sequence from the Fucino Basin: new insights into the major explosive events in Italy

NASA Astrophysics Data System (ADS)

Di Roberto, Alessio; Smedile, Alessandra; Del Carlo, Paola; De Martini, Paolo Marco; Iorio, Marina; Petrelli, Maurizio; Pantosti, Daniela; Pinzi, Stefania; Todrani, Alessandro

2018-03-01

Two cores were sampled in the Fucino Basin (central Apennines, Italy), which represents an extensional intramountain basin filled by Pliocene to Quaternary continental alluvial and lacustrine deposits. The cores were investigated for tephra content and five visible tephras with thickness ranging from 1 to 8 cm were identified. Six additional cryptotephra were identified during the inspection of significant peaks of the magnetic susceptibility curve. Texture and mineralogy of five tephra and six cryptotephra layers were analyzed by means of scanning electron microscope coupled with energy-dispersive X-ray spectrometry system (SEM-EDS) and geochemical measurements were performed by an electron microprobe (EPMA) equipped with five wavelength-dispersive spectrometers (WDS) and using a laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) system on single glass shards. The results allowed us to assign tephra and cryptotephra to ten known volcanic eruptions that occurred over the last ca. 60 ka in the Campanian Province (Phlegrean Fields and Ischia Island), the Alban Hills volcanic complex, and Lipari island. In particular, we recognized the deposits of the Monte Epomeo Green Tuff and the Piroclastiti di Catavola eruptions of Ischia, the pre-Campanian Ignimbrite Tlc, the Campanian Ignimbrite and the Neapolitan Yellow Tuff eruptions of the Phlegrean Fields, the Gabellotto-Fiume Bianco eruption of Lipari, and all the four explosive events belonging to the last cycle of volcanic activity of Albano maar (Albano 4-7). Deposits from five of these identified events (i.e., Piroclastiti di Catavola, Gabellotto-Fiume Bianco, Albano 5 and 6 eruptions, and Campanian Ignimbrite) were previously un-reported in the Fucino basin. These findings add new tephra layers to the list of possible tephrochronologic markers in the region and highlight that a comprehensive tephra record may be constructed when the study of cryptotephra layers is included. Moreover, results provide insights into the most recent volcanic activity of Albano maar, allowing us to date the onset of activity at the maar system at ca. 40 ka and to estimate the ages of all four eruptions that made up this eruptive sequence at ca. 37.5 ka (Albano 5), ca. 36.5 ka (Albano 6) and ca. 36 ka (Albano 7), respectively. Our work extends the known dispersal of several major explosive events, suggesting the intensity and magnitude appraisals, and attended risk scenario's need to be revised using improved records of distal fall out.

75 FR 6162 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-9-81 (MD-81), DC-9-82 (MD-82...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-08

... Corporation Model DC- 9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD-83), DC-9-87 (MD-87), and MD-88 Airplanes... Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD-83), DC-9-87 (MD-87), and MD-88 airplanes. This...., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. For service...

Md-miR156ab and Md-miR395 Target WRKY Transcription Factors to Influence Apple Resistance to Leaf Spot Disease.

PubMed

Zhang, Qiulei; Li, Yang; Zhang, Yi; Wu, Chuanbao; Wang, Shengnan; Hao, Li; Wang, Shengyuan; Li, Tianzhong

2017-01-01

MicroRNAs (miRNAs) are key regulators of gene expression that post-transcriptionally regulate transcription factors involved in plant physiological activities. Little is known about the effects of miRNAs in disease resistance in apple ( Malus × domestica ). We globally profiled miRNAs in the apple cultivar Golden Delicious (GD) infected or not with the apple leaf spot fungus Alternaria alternaria f. sp. mali (ALT1), and identified 58 miRNAs that exhibited more than a 2-fold upregulation upon ALT1 infection. We identified a pair of miRNAs that target protein-coding genes involved in the defense response against fungal pathogens; Md-miR156ab targets a novel WRKY transcription factor, MdWRKYN1, which harbors a TIR and a WRKY domain. Md-miR395 targets another transcription factor, MdWRKY26, which contains two WRKY domains. Real-time PCR analysis showed that Md-miR156ab and Md-miR395 levels increased, while MdWRKYN1 and MdWRKY26 expression decreased in ALT1-inoculated GD leaves; furthermore, the overexpression of Md-miR156ab and Md-miR395 resulted in a significant reduction in MdWRKYN1 and MdWRKY26 expression. To investigate whether these miRNAs and their targets play a crucial role in plant defense, we overexpressed MdWRKYN1 or knocked down Md-miR156ab activity, which in both cases enhanced the disease resistance of the plants by upregulating the expression of the WRKY-regulated pathogenesis-related (PR) protein-encoding genes MdPR3-1, MdPR3-2, MdPR4, MdPR5, MdPR10-1 , and MdPR10-2 . In a similar analysis, we overexpressed MdWRKY26 or suppressed Md-miR395 activity, and found that many PR protein-encoding genes were also regulated by MdWRKY26 . In GD, ALT-induced Md-miR156ab and Md-miR395 suppress MdWRKYN1 and MdWRKY26 expression, thereby decreasing the expression of some PR genes, and resulting in susceptibility to ALT1.

Apple MdACS6 Regulates Ethylene Biosynthesis During Fruit Development Involving Ethylene-Responsive Factor.

PubMed

Li, Tong; Tan, Dongmei; Liu, Zhi; Jiang, Zhongyu; Wei, Yun; Zhang, Lichao; Li, Xinyue; Yuan, Hui; Wang, Aide

2015-10-01

Ethylene biosynthesis in plants involves different 1-aminocyclopropane-1-carboxylic acid synthase (ACS) genes. The regulation of each ACS gene during fruit development is unclear. Here, we characterized another apple (Malus×domestica) ACS gene, MdACS6. The transcript of MdACS6 was observed not only in fruits but also in other tissues. During fruit development, MdACS6 was initiated at a much earlier stage, whereas MdACS3a and MdACS1 began to be expressed at 35 d before harvest and immediateley after harvest, respectively. Moreover, the enzyme activity of MdACS6 was significantly lower than that of MdACS3a and MdACS1, accounting for the low ethylene biosynthesis in young fruits. Overexpression of MdACS6 (MdACS6-OE) by transient assay in apple showed enhanced ethylene production, and MdACS3a was induced in MdACS6-OE fruits but not in control fruits. In MdACS6 apple fruits silenced by the virus-induced gene silencing (VIGS) system (MdACS6-AN), neither ethylene production nor MdACS3a transcript was detectable. In order to explore the mechanism through which MdACS3a was induced in MdACS6-OE fruits, we investigated the expression of apple ethylene-responsive factor (ERF) genes. The results showed that the expression of MdERF2 was induced in MdACS6-OE fruits and inhibited in MdACS6-AN fruits. Yeast one-hybrid assay showed that MdERF2 protein could bind to the promoter of MdACS3a. Moreover, down-regulation of MdERF2 in apple flesh callus led to a decrease of MdACS3a expression, demonstrating the regulation of MdERF2 on MdACS3a. The mechanism through which MdACS6 regulates the action of MdACS3a was discussed. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A Comparison of HAART Outcomes between the US Military HIV Natural History Study (NHS) and HIV Atlanta Veterans Affairs Cohort Study (HAVACS)

DTIC Science & Technology

2013-05-01

Acknowledgments The IDCRP HIV Working Group includes: Susan Banks, RN, CAPT Mary Bavaro, MD, Ionut Bebu, PhD, Helen Chun, MD, Nancy Crum- Cianflone, MD, MPH...Cathy Decker, MD, Conner Eggleston, LTC Tomas Ferguson, MD, COL Susan Fraser, MD, MAJ Joshua Hartzell, MD, MAJ Joshua Hawley, MD, LTC Gunther Hsue, MD

The Jasmonate-Activated Transcription Factor MdMYC2 Regulates ETHYLENE RESPONSE FACTOR and Ethylene Biosynthetic Genes to Promote Ethylene Biosynthesis during Apple Fruit Ripening[OPEN

PubMed Central

Xu, Yaxiu; Zhang, Lichao; Ji, Yinglin; Tan, Dongmei; Yuan, Hui

2017-01-01

The plant hormone ethylene is critical for ripening in climacteric fruits, including apple (Malus domestica). Jasmonate (JA) promotes ethylene biosynthesis in apple fruit, but the underlying molecular mechanism is unclear. Here, we found that JA-induced ethylene production in apple fruit is dependent on the expression of MdACS1, an ACC synthase gene involved in ethylene biosynthesis. The expression of MdMYC2, encoding a transcription factor involved in the JA signaling pathway, was enhanced by MeJA treatment in apple fruits, and MdMYC2 directly bound to the promoters of both MdACS1 and the ACC oxidase gene MdACO1 and enhanced their transcription. Furthermore, MdMYC2 bound to the promoter of MdERF3, encoding a transcription factor involved in the ethylene-signaling pathway, thereby activating MdACS1 transcription. We also found that MdMYC2 interacted with MdERF2, a suppressor of MdERF3 and MdACS1. This protein interaction prevented MdERF2 from interacting with MdERF3 and from binding to the MdACS1 promoter, leading to increased transcription of MdACS1. Collectively, these results indicate that JA promotes ethylene biosynthesis through the regulation of MdERFs and ethylene biosynthetic genes by MdMYC2. PMID:28550149

The Jasmonate-Activated Transcription Factor MdMYC2 Regulates ETHYLENE RESPONSE FACTOR and Ethylene Biosynthetic Genes to Promote Ethylene Biosynthesis during Apple Fruit Ripening.

PubMed

Li, Tong; Xu, Yaxiu; Zhang, Lichao; Ji, Yinglin; Tan, Dongmei; Yuan, Hui; Wang, Aide

2017-06-01

The plant hormone ethylene is critical for ripening in climacteric fruits, including apple ( Malus domestica ). Jasmonate (JA) promotes ethylene biosynthesis in apple fruit, but the underlying molecular mechanism is unclear. Here, we found that JA-induced ethylene production in apple fruit is dependent on the expression of MdACS1 , an ACC synthase gene involved in ethylene biosynthesis. The expression of MdMYC2 , encoding a transcription factor involved in the JA signaling pathway, was enhanced by MeJA treatment in apple fruits, and MdMYC2 directly bound to the promoters of both MdACS1 and the ACC oxidase gene MdACO1 and enhanced their transcription. Furthermore, MdMYC2 bound to the promoter of MdERF3 , encoding a transcription factor involved in the ethylene-signaling pathway, thereby activating MdACS1 transcription. We also found that MdMYC2 interacted with MdERF2, a suppressor of MdERF3 and MdACS1 This protein interaction prevented MdERF2 from interacting with MdERF3 and from binding to the MdACS1 promoter, leading to increased transcription of MdACS1 Collectively, these results indicate that JA promotes ethylene biosynthesis through the regulation of MdERFs and ethylene biosynthetic genes by MdMYC2. © 2017 American Society of Plant Biologists. All rights reserved.

Apple FLOWERING LOCUS T proteins interact with transcription factors implicated in cell growth and organ development.

PubMed

Mimida, Naozumi; Kidou, Shin-Ichiro; Iwanami, Hiroshi; Moriya, Shigeki; Abe, Kazuyuki; Voogd, Charlotte; Varkonyi-Gasic, Erika; Kotoda, Nobuhiro

2011-05-01

Understanding the flowering process in apple (Malus × domestica Borkh.) is essential for developing methods to shorten the breeding period and regulate fruit yield. It is known that FLOWERING LOCUS T (FT) acts as a transmissible floral inducer in the Arabidopsis flowering network system. To clarify the molecular network of two apple FT orthologues, MdFT1 and MdFT2, we performed a yeast two-hybrid screen to identify proteins that interact with MdFT1. We identified several transcription factors, including two members of the TCP (TEOSINTE BRANCHED1, CYCLOIDEA and PROLIFERATING CELL FACTORs) family, designated MdTCP2 and MdTCP4, and an Arabidopsis thaliana VOZ1 (Vascular plant One Zinc finger protein1)-like protein, designated MdVOZ1. MdTCP2 and MdVOZ1 also interacted with MdFT2 in yeast. The expression domain of MdTCP2 and MdVOZ1 partially overlapped with that of MdFT1 and MdFT2, most strikingly in apple fruit tissue, further suggesting a potential interaction in vivo. Constitutive expression of MdTCP2, MdTCP4 and MdVOZ1 in Arabidopsis affected plant size, leaf morphology and the formation of leaf primordia on the adaxial side of cotyledons. On the other hand, chimeric MdTCP2, MdTCP4 and MdVOZ1 repressors that included the ethylene-responsive transcription factors (ERF)-associated amphiphilic repression (EAR) domain motif influenced reproduction and inflorescence architecture in transgenic Arabidopsis. These results suggest that MdFT1 and/or MdFT2 might be involved in the regulation of cellular proliferation and the formation of new tissues and that they might affect leaf and fruit development by interacting with TCP- and VOZ-family proteins. DDBJ accession nos. AB531019 (MdTCP2a mRNA), AB531020 (MdTCP2b mRNA), AB531021 (MdTCP4a mRNA), AB531022 (MdTCP4b mRNA) and AB531023 (MdVOZ1a mRNA). © The Author 2011. Published by Oxford University Press. All rights reserved.

Exploring intentions of physician-scientist trainees: factors influencing MD and MD/PhD interest in research careers.

PubMed

Kwan, Jennifer M; Daye, Dania; Schmidt, Mary Lou; Conlon, Claudia Morrissey; Kim, Hajwa; Gaonkar, Bilwaj; Payne, Aimee S; Riddle, Megan; Madera, Sharline; Adami, Alexander J; Winter, Kate Quinn

2017-07-11

Prior studies have described the career paths of physician-scientist candidates after graduation, but the factors that influence career choices at the candidate stage remain unclear. Additionally, previous work has focused on MD/PhDs, despite many physician-scientists being MDs. This study sought to identify career sector intentions, important factors in career selection, and experienced and predicted obstacles to career success that influence the career choices of MD candidates, MD candidates with research-intense career intentions (MD-RI), and MD/PhD candidates. A 70-question survey was administered to students at 5 academic medical centers with Medical Scientist Training Programs (MSTPs) and Clinical and Translational Science Awards (CTSA) from the NIH. Data were analyzed using bivariate or multivariate analyses. More MD/PhD and MD-RI candidates anticipated or had experienced obstacles related to balancing academic and family responsibilities and to balancing clinical, research, and education responsibilities, whereas more MD candidates indicated experienced and predicted obstacles related to loan repayment. MD/PhD candidates expressed higher interest in basic and translational research compared to MD-RI candidates, who indicated more interest in clinical research. Overall, MD-RI candidates displayed a profile distinct from both MD/PhD and MD candidates. MD/PhD and MD-RI candidates experience obstacles that influence their intentions to pursue academic medical careers from the earliest training stage, obstacles which differ from those of their MD peers. The differences between the aspirations of and challenges facing MD, MD-RI and MD/PhD candidates present opportunities for training programs to target curricula and support services to ensure the career development of successful physician-scientists.

Growth Failure in Children with Kidney Disease

MedlinePlus

... Ira Davis, M.D.; Ann Guillott, M.D.; Steve Alexander, M.D.; Deborah Kees-Folts, M.D.; Alicia Neu, M.D.; Steve Wassner, M.D.; John Brandt, M.D.; and ... Coordinating Committees Strategic Plans & Reports Research Areas FAQs Jobs at NIDDK Visit Us Contact Us News News ...

A Conversation Among the IAS-USA Board of Directors: Hot Topics and Emerging Data in HIV Research and Care.

PubMed

Benson, Constance A; Currier, Judith S; Del Rio, Carlos; Gallant, Joel E; Gulick, Roy M; Marrazzo, Jeanne M; Richman, Douglas D; Saag, Michael S; Schooley, Robert T; Volberding, Paul A

The IAS-USA volunteer Board of Directors met in October 2016 for its annual meeting. For the second year, the Board conducted a live, hour-long, interactive, roundtable webinar covering current questions and issues in HIV research, prevention, and care. Important highlights from the Board's discussion, which was moderated by Paul A. Volberding, MD, are included below. Members of the IAS-USA volunteer Board of Directors are Constance A. Benson, MD; Judith S. Currier, MD; Carlos del Rio, MD; Joel E. Gallant, MD, MPH; Roy M. Gulick, MD, MPH; Jeanne M. Marrazzo, MD, MPH; Douglas D. Richman, MD; Michael S. Saag, MD; Robert T. Schooley, MD; and Paul A. Volberding, MD.

Apple (Malus domestica) MdERF2 negatively affects ethylene biosynthesis during fruit ripening by suppressing MdACS1 transcription.

PubMed

Li, Tong; Jiang, Zhongyu; Zhang, Lichao; Tan, Dongmei; Wei, Yun; Yuan, Hui; Li, Tianlai; Wang, Aide

2016-12-01

Ripening in climacteric fruit requires the gaseous phytohormone ethylene. Although ethylene signaling has been well studied, knowledge of the transcriptional regulation of ethylene biosynthesis is still limited. Here we show that an apple (Malus domestica) ethylene response factor, MdERF2, negatively affects ethylene biosynthesis and fruit ripening by suppressing the transcription of MdACS1, a gene that is critical for biosynthesis of ripening-related ethylene. Expression of MdERF2 was suppressed by ethylene during ripening of apple fruit, and we observed that MdERF2 bound to the promoter of MdACS1 and directly suppressed its transcription. Moreover, MdERF2 suppressed the activity of the promoter of MdERF3, a transcription factor that we found to bind to the MdACS1 promoter, thereby increasing MdACS1 transcription. We determined that the MdERF2 and MdERF3 proteins directly interact, and this interaction suppresses the binding of MdERF3 to the MdACS1 promoter. Moreover, apple fruit with transiently downregulated MdERF2 expression showed higher ethylene production and faster ripening. Our results indicate that MdERF2 negatively affects ethylene biosynthesis and fruit ripening in apple by suppressing the transcription of MdACS1 via multiple mechanisms, thereby acting as an antagonist of positive ripening regulators. Our findings offer a deep understanding of the transcriptional regulation of ethylene biosynthesis during climacteric fruit ripening. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Lessons from anti-thalassemia campaigns in Italy, before prenatal diagnosis.

PubMed

Canali, Stefano; Corbellini, Gilberto

2002-01-01

The essay reconstructs the antithalassemia campaign carried out by means of population screening and pre-marriage counseling for about twenty years in Italy, immediately after the relationship between microcythemia and Cooley's anemia had been established, as well as its genetic bases. We examine the Italian contributions to the understanding of the genetics and of the clinical treatment of thalassemic disorders, and analyze the approaches to prevention as well as the results obtained by the first campaign against a genetic disease, conceived and largely implemented in Italy by Ezio Silvestroni and Ida Bianco. We discuss the resistances met by the antithalassemia campaign due to the cultural and organizational backwardness of the Italian medical community and of the public health system. Moreover we analyze the explanations and interpretations of the problematic results of these experiences in terms of morbidity reduction. It will be pointed out that the objective of genetic counselling practised in that context assumed the concept of disease prevention at the population level, and it was far from the idea, emerged in the 1970s, of non directive genetic counselling.

KSC-98pc1629

NASA Image and Video Library

1998-11-10

KENNEDY SPACE CENTER, FLA. -- In the Spacecraft Assembly and Encapsulation Facility-2 (SAEF-2), Tandy Bianco, with Lockheed Martin, and Satish Krishnan (foreground) and Chris Voorhees (behind him), from the Jet Propulsion Laboratory, observe a Mars microprobe on the workstand. Two microprobes will hitchhike on the Mars Polar Lander, scheduled to be launched Jan. 3, 1999, aboard a Delta II rocket. The solar-powered spacecraft is designed to touch down on the Martian surface near the northern-most boundary of the south pole in order to study the water cycle there. The lander also will help scientists learn more about climate change and current resources on Mars, studying such things as frost, dust, water vapor and condensates in the Martian atmosphere. The Mars microprobes, called Deep Space 2, are part of NASA's New Millelnnium Program. They will complement the climate-related scientific focus of the lander by demonstrating an advanced, rugged microlaser system for detecting subsurface water. Such data on polar subsurface water, in the form of ice, should help put limits on scientific projections for the global abundance of water on Mars

Apple RING E3 ligase MdMIEL1 inhibits anthocyanin accumulation by ubiquitinating and degrading MdMYB1 protein.

PubMed

An, Jian-Ping; Liu, Xin; Li, Hao-Hao; You, Chun-Xiang; Wang, Xiao-Fei; Hao, Yu-Jin

2017-11-01

MdMYB1 is an important regulator for anthocyanin accumulation in apple (Malus × domestica). Here, an apple RING E3 ligase, MdMIEL1, was screened out as a partner of MdMYB1 with a yeast two-hybrid approach. Pull-down, bimolecular fluorescence complementation and coimmunoprecipitation assays further verified the interaction between MdMIEL1 and MdMYB1 proteins. Subsequently, in vitro and in vivo experiments indicated that MdMIEL1 functioned as a ubiquitin E3 ligase to ubiquitinate MdMYB1 protein, followed by degradation through a 26S proteasome pathway. Furthermore, transgenic studies in apple calli and Arabidopsis demonstrated that MdMIEL1 negatively regulated anthocyanin accumulation by modulating the degradation of MdMYB1 protein. Taken together, our findings provide a new insight into the molecular mechanism by which MdMIEL1 negatively regulates anthocyanin biosynthesis by ubiquitinating and degrading MdMYB1 protein. © 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 R2R3-MYB transcription factor MdMYB73 is involved in malate accumulation and vacuolar acidification in apple.

PubMed

Hu, Da-Gang; Li, Yuan-Yuan; Zhang, Quan-Yan; Li, Ming; Sun, Cui-Hui; Yu, Jian-Qiang; Hao, Yu-Jin

2017-08-01

Malate, the predominant organic acid in many fruits, is a crucial component of the organoleptic quality of fruit, including taste and flavor. The genetic and environmental mechanisms affecting malate metabolism in fruit cells have been studied extensively. However, the transcriptional regulation of malate-metabolizing enzymes and vacuolar transporters remains poorly understood. Our previous studies demonstrated that MdMYB1 modulates anthocyanin accumulation and vacuolar acidification by directly activating vacuolar transporters, including MdVHA-B1, MdVHA-E, MdVHP1 and MdtDT. Interestingly, we isolated and identified a MYB transcription factor, MdMYB73, a distant relative of MdMYB1 in this study. It was subsequently found that MdMYB73 protein bound directly to the promoters of MdALMT9 (aluminum-activated malate transporter 9), MdVHA-A (vacuolar ATPase subunit A) and MdVHP1 (vacuolar pyrophosphatase 1), transcriptionally activating their expression and thereby enhancing their activities. Analyses of transgenic apple calli demonstrated that MdMYB73 influenced malate accumulation and vacuolar pH. Furthermore, MdCIbHLH1 interacted with MdMYB73 and enhanced its activity upon downstream target genes. These findings help to elucidate how MdMYB73 directly modulates the vacuolar transport system to affect malate accumulation and vacuolar pH in apple. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

MdSOS2L1 phosphorylates MdVHA-B1 to modulate malate accumulation in response to salinity in apple.

PubMed

Hu, Da-Gang; Sun, Cui-Hui; Sun, Mei-Hong; Hao, Yu-Jin

2016-03-01

Salt-induced phosphorylation of MdVHA-B1 protein was mediated by MdSOS2L1 protein kinase, and thereby increasing malate content in apple. Salinity is an important environmental factor that influences malate accumulation in apple. However, the molecular mechanism by which salinity regulates this process is poorly understood. In this work, we found that MdSOS2L1, a novel AtSOS2-LIKE protein kinase, interacts with V-ATPase subunit MdVHA-B1. Furthermore, MdSOS2L1 directly phosphorylates MdVHA-B1 at Ser(396) site to modulate malate accumulation in response to salt stress. Meanwhile, a series of transgenic analyses in apple calli showed that the MdSOS2L1-MdVHAB1 pathway was involved in the regulation of malate accumulation. Finally, a viral vector-based transformation approach demonstrated that the MdSOS2L1-MdVHAB1 pathway also modulated malate accumulation in apple fruits with or without salt stress. Collectively, our findings provide a new insight into the mechanism by which MdSOS2L1 phosphorylates MdVHA-B1 to modulate malate accumulation in response to salinity in apple.

Identification of SFBB-containing canonical and noncanonical SCF complexes in pollen of apple (Malus × domestica).

PubMed

Minamikawa, Mai F; Koyano, Ruriko; Kikuchi, Shinji; Koba, Takato; Sassa, Hidenori

2014-01-01

Gametophytic self-incompatibility (GSI) of Rosaceae, Solanaceae and Plantaginaceae is controlled by a single polymorphic S locus. The S locus contains at least two genes, S-RNase and F-box protein encoding gene SLF/SFB/SFBB that control pistil and pollen specificity, respectively. Generally, the F-box protein forms an E3 ligase complex, SCF complex with Skp1, Cullin1 (CUL1) and Rbx1, however, in Petunia inflata, SBP1 (S-RNase binding protein1) was reported to play the role of Skp1 and Rbx1, and form an SCFSLF-like complex for ubiquitination of non-self S-RNases. On the other hand, in Petunia hybrida and Petunia inflata of Solanaceae, Prunus avium and Pyrus bretschneideri of Rosaceae, SSK1 (SLF-interacting Skp1-like protein1) is considered to form the SCFSLF/SFB complex. Here, we isolated pollen-expressed apple homologs of SSK1 and CUL1, and named MdSSK1, MdCUL1A and MdCUL1B. MdSSK1 was preferentially expressed in pollen, but weakly in other organs analyzed, while, MdCUL1A and MdCUL1B were almost equally expressed in all the organs analyzed. MdSSK1 transcript abundance was significantly (>100 times) higher than that of MdSBP1. In vitro binding assays showed that MdSSK1 and MdSBP1 interacted with MdSFBB1-S9 and MdCUL1, and MdSFBB1-S9 interacted more strongly with MdSSK1 than with MdSBP1. The results suggest that both MdSSK1-containing SCFSFBB1 and MdSBP1-containing SCFSFBB1-like complexes function in pollen of apple, and the former plays a major role.

75 FR 47199 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-9-10 Series Airplanes, DC-9-30...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-05

... Airplanes, DC-9-81 (MD-81) Airplanes, DC-9-82 (MD-82) Airplanes, DC-9-83 (MD-83) Airplanes, DC-9- 87 (MD-87...) airplanes, DC-9-87 (MD-87) airplanes, MD-88 airplanes, and MD-90-30 airplanes. That AD currently requires... INFORMATION: Discussion On June 18, 2010, we issued AD 2009-15-16, Amendment 39-16345 (75 FR 38017, July 1...

Long Range Transport of War-Related Burn Casualties

DTIC Science & Technology

2008-02-01

Long Range Transport of War-Related Burn Casualties Evan M. Renz, MD, FACS, Leopoldo C . Cancio, MD, FACS, David J. Barillo, MD, FACS, Christopher E...White, MD, FACS, Michael C . Albrecht, MD, Charles K. Thompson, PA- C , Jody L. Ennis, RN, BSN, Sandra M. Wanek, MD, James A. King, MD, FACEP, Kevin K...sched- Submitted for publication October 29, 2007. Accepted for publication October 30, 2007. Copyright © 2008 by Lippincott Williams & Wilkins From the

Scheduling of eccentric lower limb injury prevention exercises during the soccer micro-cycle: Which day of the week?

PubMed

Lovell, R; Whalan, M; Marshall, P W M; Sampson, J A; Siegler, J C; Buchheit, M

2018-05-24

Scheduling eccentric-based injury prevention programs (IPP) during the common 6-day micro-cycle in soccer is challenged by recovery and tapering phases. This study profiled muscle damage, neuromuscular performance, and perceptual responses to a lower limb eccentric-based IPP administered 1 (MD+1) vs 3 days (MD+3) postmatch. A total of 18 semi-professional players were monitored daily during 3 in-season 6-day micro-cycles, including weekly competitive fixtures. Capillary creatine kinase concentration (CK), posterior lower limb isometric peak force (PF), counter-movement jump (CMJ) performance, and muscle soreness were assessed 24 hours prior to match-day (baseline), and every 24 hours up to 120 hours postmatch. The IPP consisted of lunges, single stiff leg dead-lifts, single leg-squats, and Nordic hamstring exercises. Performing the IPP on MD+1 attenuated the decline in CK normally observed following match play (CON: 142%; MD+3: 166%; small differences). When IPP was delivered on MD+3, CK was higher vs CON and MD+1 trials on both MD+4 (MD+3: 260%; CON: 146%; MD+1: 151%; moderate differences) and MD+5 (MD+3: 209%; CON: 125%; MD+1: 127%; small differences). Soreness ratings were not exacerbated when the IPP was delivered on MD+1, but when prescribed on MD+3, hamstring soreness ratings remained higher on MD+4 and MD+5 (small differences). No between-trial differences were observed for PF and CMJ. Administering the IPP in the middle of the micro-cycle (MD+3) increased measures of muscle damage and soreness, which remained elevated on the day prior to the next match (MD+5). Accordingly, IPP should be scheduled early in the micro-cycle, to avoid compromising preparation for the following match. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Microdialysis Monitoring of CSF Parameters in Severe Traumatic Brain Injury Patients: A Novel Approach

PubMed Central

Thelin, Eric P.; Nelson, David W.; Ghatan, Per Hamid; Bellander, Bo-Michael

2014-01-01

Background: Neuro-intensive care following traumatic brain injury (TBI) is focused on preventing secondary insults that may lead to irreversible brain damage. Microdialysis (MD) is used to detect deranged cerebral metabolism. The clinical usefulness of the MD is dependent on the regional localization of the MD catheter. The aim of this study was to analyze a new method of continuous cerebrospinal fluid (CSF) monitoring using the MD technique. The method was validated using conventional laboratory analysis of CSF samples. MD-CSF and regional MD-Brain samples were correlated to patient outcome. Materials and Methods: A total of 14 patients suffering from severe TBI were analyzed. They were monitored using (1) a MD catheter (CMA64-iView, n = 7448 MD samples) located in a CSF-pump connected to the ventricular drain and (2) an intraparenchymal MD catheter (CMA70, n = 8358 MD samples). CSF-lactate and CSF-glucose levels were monitored and were compared to MD-CSF samples. MD-CSF and MD-Brain parameters were correlated to favorable (Glasgow Outcome Score extended, GOSe 6–8) and unfavorable (GOSe 1–5) outcome. Results: Levels of glucose and lactate acquired with the CSF-MD technique could be correlated to conventional levels. The median MD recovery using the CMA64 catheter in CSF was 0.98 and 0.97 for glucose and lactate, respectively. Median MD-CSF (CMA 64) lactate (p = 0.0057) and pyruvate (p = 0.0011) levels were significantly lower in the favorable outcome group compared to the unfavorable group. No significant difference in outcome was found using the lactate:pyruvate ratio (LPR), or any of the regional MD-Brain monitoring in our analyzed cohort. Conclusion: This new technique of global MD-CSF monitoring correlates with conventional CSF levels of glucose and lactate, and the MD recovery is higher than previously described. Increase in lactate and pyruvate, without any effect on the LPR, correlates to unfavorable outcome, perhaps related to the presence of erythrocytes in the CSF. PMID:25228896

A dual positional specific lipoxygenase functions in the generation of flavor compounds during climacteric ripening of apple

PubMed Central

Schiller, Doreen; Contreras, Carolina; Vogt, Jörg; Dunemann, Frank; Defilippi, Bruno G; Beaudry, Randolph; Schwab, Wilfried

2015-01-01

Lipoxygenase (LOX) is an important contributor to the formation of aroma-active C6 aldehydes in apple (Malus × domestica) fruit upon tissue disruption but little is known about its role in autonomously produced aroma volatiles from intact tissue. We explored the expression of 22 putative LOX genes in apple throughout ripening, but only six LOXs were expressed in a ripening-dependent manner. Recombinant LOX1:Md:1a, LOX1:Md:1c, LOX2:Md:2a and LOX2:Md:2b proteins showed 13/9-LOX, 9-LOX, 13/9-LOX and 13-LOX activity with linoleic acid, respectively. While products of LOX1:Md:1c and LOX2:Md:2b were S-configured, LOX1:Md:1a and LOX2:Md:2a formed 13(R)-hydroperoxides as major products. Site-directed mutagenesis of Gly567 to an alanine converted the dual positional specific LOX1:Md:1a to an enzyme with a high specificity for 9(S)-hydroperoxide formation. The high expression level of the corresponding MdLOX1a gene in stored apple fruit, the genetic association with a quantitative trait locus for fruit ester and the remarkable agreement in regio- and stereoselectivity of the LOX1:Md:1a reaction with the overall LOX activity found in mature apple fruits, suggest a major physiological function of LOX1:Md:1a during climacteric ripening of apples. While LOX1:Md:1c, LOX2:Md:2a and LOX2:Md:2b may contribute to aldehyde production in immature fruit upon cell disruption our results furnish additional evidence that LOX1:Md:1a probably regulates the availability of precursors for ester production in intact fruit tissue. PMID:26504564

MdCOP1 Ubiquitin E3 Ligases Interact with MdMYB1 to Regulate Light-Induced Anthocyanin Biosynthesis and Red Fruit Coloration in Apple1[W][OA

PubMed Central

Li, Yuan-Yuan; Mao, Ke; Zhao, Cheng; Zhao, Xian-Yan; Zhang, Hua-Lei; Shu, Huai-Rui; Hao, Yu-Jin

2012-01-01

MdMYB1 is a crucial regulator of light-induced anthocyanin biosynthesis and fruit coloration in apple (Malus domestica). In this study, it was found that MdMYB1 protein accumulated in the light but degraded via a ubiquitin-dependent pathway in the dark. Subsequently, the MdCOP1-1 and MdCOP1-2 genes were isolated from apple fruit peel and were functionally characterized in the Arabidopsis (Arabidopsis thaliana) cop1-4 mutant. Yeast (Saccharomyces cerevisiae) two-hybrid, bimolecular fluorescence complementation, and coimmunoprecipitation assays showed that MdMYB1 interacts with the MdCOP1 proteins. Furthermore, in vitro and in vivo experiments indicated that MdCOP1s are necessary for the ubiquitination and degradation of MdMYB1 protein in the dark and are therefore involved in the light-controlled stability of the MdMYB1 protein. Finally, a viral vector-based transformation approach demonstrated that MdCOP1s negatively regulate the peel coloration of apple fruits by modulating the degradation of the MdMYB1 protein. Our findings provide new insight into the mechanism by which light controls anthocyanin accumulation and red fruit coloration in apple and even other plant species. PMID:22855936

Cognitive arithmetic and problem solving: a comparison of children with specific and general mathematics difficulties.

PubMed

Jordan, N C; Montani, T O

1997-01-01

This study examined problem-solving and number-fact skills in two subgroups of third-grade children with mathematics difficulties (MD): MD-specific (n = 12) and MD-general (n = 12). The MD-specific group had difficulties in mathematics but not in reading, and the MD-general group had difficulties in reading as well as in mathematics. A comparison group of nonimpaired children (n = 24) also was included. The findings showed that on both story and number-fact problems, the MD-specific group performed worse than the nonimpaired group in timed conditions but not in untimed conditions. The MD-general group, on the other hand, performed worse than the nonimpaired group, regardless of whether tasks were timed or not. An analysis of children's strategies in untimed conditions showed that both the MD-specific and the MD-general groups relied more on backup strategies than the nonimpaired group. However, children in the MD-specific group executed backup strategies more skillfully than children in the MD-general group, allowing them to achieve parity with children in the nonimpaired group when tasks were not timed. The findings suggest that children with specific MD have circumscribed deficits associated with fact retrieval, whereas children with general MD have more basic delays associated with problem conceptualization and execution of calculation procedures.

Development of a Free-Electron Laser Center and Research in Medicine, Biology and Materials Science,

DTIC Science & Technology

1992-05-14

Elastin Production in Tissue Culture", Debra A.Gonzalez MD, David L. Zealear, PhD., J.M. Davidson, PhD., Robert H. Ossoff, MD, DMD , August 1990...Otolaryngoloty-Head and Neck Surgery. K. "CO2 Laser Micromanipulator Parallax Error Resolved, Jay Werkhaven,MD, Jerri Tribble, and Robert H. Ossoff, MD, DMD ...of the Upper Aerodigestive Tract, Robert H. Ossoff, MD, DMD , Al Aly, MD, Nick Houchin, AAS, and Debra Gonzalez, MD, Vanderbilt University, Nashville

Medical Department, United States Army. Surgery in World War 2. Neurosurgery. Volume 2

DTIC Science & Technology

1959-01-01

that there was no obstruction distal to the opening. They might close spontaneously in either area. If the fistula was small and spontaneous closure did...States Army Editor in Chief Colonel JOHN BOYD COATES, Jr ., MC Editors for Neurosurgery R. GLEN SPURLING, M.D. BARNES WOODHALL, M.D. Associate Editor...M.D. M. ELAOT RANDOLPH, M.D. STERLING BUNNELL, M.D. (dec.) ISIDOR S. RAVDIN, M.D. NORTON CANFIELD, M.D. ALFRED R. SHANDS, Jr ., M.D. B. NOLAND CARTER

Prematch salivary secretory immunoglobulin a in soccer players from the 2014 World Cup qualifying campaign.

PubMed

Morgans, Ryland; Owen, Adam; Doran, Dominic; Drust, Barry; Morton, James P

2015-04-01

To monitor resting salivary secretory immunoglobulin A (SIgA) levels in international soccer players during the short-term training period that precedes international match play. In a repeated-measure design, saliva samples were obtained from 13 outfield soccer players who participated in the training camps preceding 7 games (5 home and 2 away) of the 2014 FIFA World Cup qualifying campaign. Samples were obtained daily for 4 d preceding each game (and analyzed for SIgA using the IPRO oral-fluid-collection system) at match day minus 1 (MD-1), minus 2 (MD-2), minus 3 (MD-3), and minus 4 (MD-4). SIgA displayed a progressive decline (P = .01) during the 4-d training period (MD-4, 365 ± 127 μg/mL; MD-3, 348 ± 154 μg/mL; MD-2, 290 ± 138 μg/mL; MD-1, 256 ± 90 μg/mL) such that MD-1 values were significantly lower (P = .01) than both MD-4 and MD-3. The 95% confidence intervals for the differences between MD-1 and MD-4 were -191 to -26 and between MD-1 and MD-3 were -155 to -28. Data demonstrate that a short-term soccer-training camp in preparation for international competition induces detectable perturbations to mucosal immunity. Future studies should monitor SIgA (as a practical and noninvasive measure of immunity) alongside internal and external measures of training load in an attempt to strategically individualize training and nutritional strategies that may support optimal preparation for high-level competition.

Improved Statistical Sampling and Accuracy with Accelerated Molecular Dynamics on Rotatable Torsions.

PubMed

Doshi, Urmi; Hamelberg, Donald

2012-11-13

In enhanced sampling techniques, the precision of the reweighted ensemble properties is often decreased due to large variation in statistical weights and reduction in the effective sampling size. To abate this reweighting problem, here, we propose a general accelerated molecular dynamics (aMD) approach in which only the rotatable dihedrals are subjected to aMD (RaMD), unlike the typical implementation wherein all dihedrals are boosted (all-aMD). Nonrotatable and improper dihedrals are marginally important to conformational changes or the different rotameric states. Not accelerating them avoids the sharp increases in the potential energies due to small deviations from their minimum energy conformations and leads to improvement in the precision of RaMD. We present benchmark studies on two model dipeptides, Ace-Ala-Nme and Ace-Trp-Nme, simulated with normal MD, all-aMD, and RaMD. We carry out a systematic comparison between the performances of both forms of aMD using a theory that allows quantitative estimation of the effective number of sampled points and the associated uncertainty. Our results indicate that, for the same level of acceleration and simulation length, as used in all-aMD, RaMD results in significantly less loss in the effective sample size and, hence, increased accuracy in the sampling of φ-ψ space. RaMD yields an accuracy comparable to that of all-aMD, from simulation lengths 5 to 1000 times shorter, depending on the peptide and the acceleration level. Such improvement in speed and accuracy over all-aMD is highly remarkable, suggesting RaMD as a promising method for sampling larger biomolecules.

Apple fruit acidity is genetically diversified by natural variations in three hierarchical epistatic genes MdSAUR37, MdPP2CH and MdALMTII.

PubMed

Jia, Dongjie; Shen, Fei; Wang, Yi; Wu, Ting; Xu, Xuefeng; Zhang, Xinzhong; Han, Zhenhai

2018-05-11

Many efforts have been made to map quantitative trait loci (QTLs) to facilitate practical marker-assisted selection (MAS) in plants. In the present study, we identified four genome-wide major QTLs responsible for apple fruit acidity by MapQTL and BSA-seq analyses using two independent pedigree-based populations. Candidate genes were screened in major QTL regions, and three functional gene markers, including a non-synonymous A/G single nucleotide polymorphism (SNP) in the coding region of MdPP2CH, a 36-bp insertion in the promoter of MdSAUR37, and a previously reported SNP in MdALMTII, were validated to influence the malate content of apple fruits. In addition, MdPP2CH inactivated three vacuolar H + -ATPases (MdVHA-A3, MdVHA-B2 and MdVHA-D2) and one aluminium-activated malate transporter (MdALMTII) via dephosphorylation and negatively influenced fruit malate accumulation. The dephosphotase activity of MdPP2CH was suppressed by MdSAUR37, which implied a higher hierarchy of genetic interaction. Therefore, the MdSAUR37/MdPP2CH/MdALMTII chain cascaded hierarchical epistatic genetic effects to precisely determine apple fruit malate content. An A/G SNP (-1010) on MdMYB44 promoter region from a major QTL (qtl08.1) was closely associated with fruit malate content. The predicted phenotype values (PPVs) were estimated using the tentative genotype values of the gene markers, and the PPVs were significantly correlated with the observed phenotype values. Our findings provide an insight into plant genome-based selection in apples and will aid in conducting research to understand the physiological fundamentals of quantitative genetics. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

An Apple Protein Kinase MdSnRK1.1 Interacts with MdCAIP1 to Regulate ABA Sensitivity.

PubMed

Liu, Xiao-Juan; Liu, Xin; An, Xiu-Hong; Han, Peng-Liang; You, Chun-Xiang; Hao, Yu-Jin

2017-10-01

ABA is a crucial phytohormone for development and stress responses in plants. Snf1-related protein kinase 1.1 (SnRK1.1) is involved in the ABA response. However, the molecular mechanism underlying the SnRK1.1 response to ABA is largely unknown. Here, it was found that overexpression of the apple MdSnRK1.1 gene enhanced ABA sensitivity in both transgenic apple calli and Arabidopsis seedlings. Subsequently, a yeast two-hybrid screen demonstrated that MdCAIP1 (C2-domain ABA Insensitive Protein1) interacted with MdSnRK1.1. Their interaction was further confirmed by pull-down and co-immunoprecipitation assays. Expression of the MdCAIP1 gene was positively induced by ABA. Its overexpression enhanced ABA sensitivity in transgenic apple calli. Furthermore, it was found that MdSnRK1.1 phosphorylated the MdCAIP1 protein in vivo and promoted its degradation in vitro and in vivo. As a result, MdSnRK1.1 inhibited MdCAIP1-mediated ABA sensitivity, and MdCAIP1 partially reduced MdSnRK1.1-mediated ABA sensitivity. Our findings indicate that MdSnRK1.1 plays an important role in the ABA response, partially by controlling the stability of the MdCAIP1 protein. © 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.

Registration of cotton germplasm USDA MD 16-1 and USDA MD 16-2 with enhanced lint yield and fiber quality.

USDA-ARS?s Scientific Manuscript database

Upland cotton germplasm USDA MD 16-1 (Reg. No. __ and PI ___ ), and USDA MD 16-2 (Reg. No. ___ and PI___) (Gossypium hirsutum L.), have enhanced yield and good fiber quality. These germplasm lines were developed by the USDA-ARS, Stoneville, MS and released in 2017. Two crosses, MD 25-51 X MD 10-9-1 ...

78 FR 14547 - Praxedes E. Alverez Santiago, M.D., Daniel Perez Brisebois, M.D., Jorge Grillasca Palou, M.D...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-06

...., Angel B. Rivera Santos, M.D., Cosme D. Santos Torres, M.D., and Juan L. Vilaro Chardon, M.D.; Analysis... attached Analysis to Aid Public Comment describes both the allegations in the draft complaint and the terms... record for a period of thirty (30) days. The following Analysis to Aid Public Comment describes the terms...

mdFoam+: Advanced molecular dynamics in OpenFOAM

NASA Astrophysics Data System (ADS)

Longshaw, S. M.; Borg, M. K.; Ramisetti, S. B.; Zhang, J.; Lockerby, D. A.; Emerson, D. R.; Reese, J. M.

2018-03-01

This paper introduces mdFoam+, which is an MPI parallelised molecular dynamics (MD) solver implemented entirely within the OpenFOAM software framework. It is open-source and released under the same GNU General Public License (GPL) as OpenFOAM. The source code is released as a publicly open software repository that includes detailed documentation and tutorial cases. Since mdFoam+ is designed entirely within the OpenFOAM C++ object-oriented framework, it inherits a number of key features. The code is designed for extensibility and flexibility, so it is aimed first and foremost as an MD research tool, in which new models and test cases can be developed and tested rapidly. Implementing mdFoam+ in OpenFOAM also enables easier development of hybrid methods that couple MD with continuum-based solvers. Setting up MD cases follows the standard OpenFOAM format, as mdFoam+ also relies upon the OpenFOAM dictionary-based directory structure. This ensures that useful pre- and post-processing capabilities provided by OpenFOAM remain available even though the fully Lagrangian nature of an MD simulation is not typical of most OpenFOAM applications. Results show that mdFoam+ compares well to another well-known MD code (e.g. LAMMPS) in terms of benchmark problems, although it also has additional functionality that does not exist in other open-source MD codes.

Optimal feeding frequency of captive head-started green turtles (Chelonia mydas).

PubMed

Kanghae, H; Thongprajukaew, K; Yeetam, P; Jarit-Ngam, T; Hwan-Air, W; Rueangjeen, S; Kittiwattanawong, K

2017-08-01

Optimal feeding frequency was investigated to improve head-started propagation programme of juvenile green turtles (Chelonia mydas). The 15-day-old turtles (25-26 g body weight) were fed for ad libitum intake at one (1MD), two (2MD), three (3MD) or four (4MD) meals daily over a 3-month trial. Responses in growth, feed utilization, faecal characteristics, haematological parameters and carapace elemental composition were used to compare treatment effects. At the end of the feeding trial, no treatment had induced mortality. Growth performance in terms of weight gain and specific growth rate was similar in turtles fed 2MD, 3MD or 4MD (p > 0.05), but 1MD differed from these (p < 0.05), and feeding at excess frequency (3MD and 4MD) increased the within-group size variation. Turtles fed 2MD had significantly lower feed intake than in 3MD and 4MD groups, but the feed conversion ratios were similar. Faecal digestive enzyme analysis indicated higher catabolism of lipid and protein in the deprivation group (1MD), when compared with turtles fed at least twice daily. The feeding frequency did not affect the specific activities of carbohydrate-digesting enzymes. The results on enzymes activities were corroborated by the transition enthalpy characteristics of faeces, indicating nutrients remaining after digestion. The 2MD treatment also improved the haematological characteristics and the carapace quality, relative to low or excess feeding. Overall, the findings indicate that feeding juvenile green turtles twice a day is the preferred option in their head-started propagation. This promotes growth, reduces feed consumption, and improves health and carapace quality. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

An apple B-box protein, MdCOL11, is involved in UV-B- and temperature-induced anthocyanin biosynthesis.

PubMed

Bai, Songling; Saito, Takanori; Honda, Chikako; Hatsuyama, Yoshimichi; Ito, Akiko; Moriguchi, Takaya

2014-11-01

Our studies showed that an apple B-box protein, MdCOL11, the homolog of AtBBX22, is involved in UV-B- and temperature-induced anthocyanin biosynthesis in apple peel. Anthocyanin is responsible for the red pigmentation in apple peel and a R2R3 MYB gene, MdMYBA/1/10, a homolog of MdMYBA, controls its accumulation. Arabidopsis PAP1 is under the control of a series of upstream factors involved in light signal transduction and photomorphogenesis, such as ELONGATED HYPOCOTYL 5 (HY5) and B-box family (BBX) proteins. In this study, we identified and characterized the homolog of Arabidopsis BBX22 in apple, designated as MdCOL11. Overexpression of MdCOL11 in Arabidopsis enhanced the accumulation of anthocyanin. In apples, MdCOL11 was differentially expressed in all tissues, with the highest expression in petals and the lowest expression in the xylem. Transcripts of MdCOL11 noticeably accumulated at the ripening stage, concomitant with increases in the expressions of anthocyanin biosynthesis-related genes. In an in vitro treatment experiment, MdCOL11 was upregulated in an ultra-violet (UV)-B- and temperature-dependent manner, together with the inductions of anthocyanin biosynthesis-related genes and anthocyanin accumulation in apple peel. Furthermore, a dual-luciferase assay indicated that (1) MdCOL11 regulated the expression of MdMYBA and (2) MdCOL11 was a target of MdHY5. Taken together, our results suggest that MdCOL11 is involved in MdHY5-mediated signal transduction and regulates anthocyanin accumulation in apple peel, which sheds new light on anthocyanin accumulation in apples.

Clinical evaluation of Morgellons disease in a cohort of North American patients

PubMed Central

Fesler, Melissa C.; Middelveen, Marianne J.; Stricker, Raphael B.

2018-01-01

Morgellons disease (MD) is a dermatological condition characterized by aberrant production of keratin and collagen fibers in skin. Although infection with Borrelia burgdorferi, the causative agent of Lyme disease (LD), has been associated with MD, relatively few studies have hitherto provided epidemiological evidence regarding this association. A cohort of 1000 seropositive North American LD patients was evaluated for the presence of MD. Patients were diagnosed with MD based on detection of microscopic fibers in skin lesions or under unbroken skin. Demographic and clinical features of MD patients were analyzed, and laboratory testing for tickborne coinfections and other infectious agents, was performed. Subjective and objective features of MD were analyzed using statistical methods. Of 1000 seropositive LD patients, 60 (6%) were diagnosed with MD. Of these 60 patients, 75% were female and 78% presented in the late disseminated stage of MD. All 60 patients (100%) were seropositive for B. burgdorferi infection. Tickborne coinfections in these patients included Babesia spp (62%), Bartonella and Rickettsia (25% each), Ehrlichia (15%) and Anaplasma (10%). Helicobacter pylori was detected in 12% of MD patients. In all, 77% of MD patients had one or more coinfections. This study confirms recent findings that MD occurs in a limited subset of LD patients. The clinical and genetic determinants of MD in LD patients require further study. PMID:29774138

Clinical evaluation of Morgellons disease in a cohort of North American patients.

PubMed

Fesler, Melissa C; Middelveen, Marianne J; Stricker, Raphael B

2018-04-23

Morgellons disease (MD) is a dermatological condition characterized by aberrant production of keratin and collagen fibers in skin. Although infection with Borrelia burgdorferi , the causative agent of Lyme disease (LD), has been associated with MD, relatively few studies have hitherto provided epidemiological evidence regarding this association. A cohort of 1000 seropositive North American LD patients was evaluated for the presence of MD. Patients were diagnosed with MD based on detection of microscopic fibers in skin lesions or under unbroken skin. Demographic and clinical features of MD patients were analyzed, and laboratory testing for tickborne coinfections and other infectious agents, was performed. Subjective and objective features of MD were analyzed using statistical methods. Of 1000 seropositive LD patients, 60 (6%) were diagnosed with MD. Of these 60 patients, 75% were female and 78% presented in the late disseminated stage of MD. All 60 patients (100%) were seropositive for B. burgdorferi infection. Tickborne coinfections in these patients included Babesia spp (62%), Bartonella and Rickettsia (25% each), Ehrlichia (15%) and Anaplasma (10%). Helicobacter pylori was detected in 12% of MD patients. In all, 77% of MD patients had one or more coinfections. This study confirms recent findings that MD occurs in a limited subset of LD patients. The clinical and genetic determinants of MD in LD patients require further study.

Comprehensive Genomic Identification and Expression Analysis of the Phosphate Transporter (PHT) Gene Family in Apple

PubMed Central

Sun, Tingting; Li, Mingjun; Shao, Yun; Yu, Lingyan; Ma, Fengwang

2017-01-01

Elemental phosphorus (Pi) is essential to plant growth and development. The family of phosphate transporters (PHTs) mediates the uptake and translocation of Pi inside the plants. Members include five sub-cellular phosphate transporters that play different roles in Pi uptake and transport. We searched the Genome Database for Rosaceae and identified five clusters of phosphate transporters in apple (Malus domestica), including 37 putative genes. The MdPHT1 family contains 14 genes while MdPHT2 has two, MdPHT3 has seven, MdPHT4 has 11, and MdPHT5 has three. Our overview of this gene family focused on structure, chromosomal distribution and localization, phylogenies, and motifs. These genes displayed differential expression patterns in various tissues. For example, expression was high for MdPHT1;12, MdPHT3;6, and MdPHT3;7 in the roots, and was also increased in response to low-phosphorus conditions. In contrast, MdPHT4;1, MdPHT4;4, and MdPHT4;10 were expressed only in the leaves while transcript levels of MdPHT1;4, MdPHT1;12, and MdPHT5;3 were highest in flowers. In general, these 37 genes were regulated significantly in either roots or leaves in response to the imposition of phosphorus and/or drought stress. The results suggest that members of the PHT family function in plant adaptations to adverse growing environments. Our study will lay a foundation for better understanding the PHT family evolution and exploring genes of interest for genetic improvement in apple. PMID:28424713

Ubiquitination-Related MdBT Scaffold Proteins Target a bHLH Transcription Factor for Iron Homeostasis1[OPEN

PubMed Central

Zhao, Qiang; Wang, Qing-Jie; Wang, Xiao-Fei; You, Chun-Xiang

2016-01-01

Iron (Fe) homeostasis is crucial for plant growth and development. A network of basic helix-loop-helix (bHLH) transcription factors positively regulates Fe uptake during iron deficiency. However, their up-regulation or overexpression leads to Fe overload and reactive oxygen species generation, thereby damaging the plants. Here, we found that two BTB/TAZ proteins, MdBT1 and MdBT2, interact with the MbHLH104 protein in apple. In addition, the function of MdBT2 was characterized as a regulator of MdbHLH104 degradation via ubiquitination and the 26S proteasome pathway, thereby controlling the activity of plasma membrane H+-ATPases and the acquisition of iron. Furthermore, MdBT2 interacted with MdCUL3 proteins, which were required for the MdBT2-mediated ubiquitination modification of MdbHLH104 and its degradation. In sum, our findings demonstrate that MdBT proteins interact with MdCUL3 to bridge the formation of the MdBTsMdCUL3 complex, which negatively modulates the degradation of the MdbHLH104 protein in response to changes in Fe status to maintain iron homeostasis in plants. PMID:27660166

MdHIR proteins repress anthocyanin accumulation by interacting with the MdJAZ2 protein to inhibit its degradation in apples

PubMed Central

Chen, Ke-Qin; Zhao, Xian-Yan; An, Xiu-Hong; Tian, Yi; Liu, Dan-Dan; You, Chun-Xiang; Hao, Yu-Jin

2017-01-01

In higher plants, jasmonate ZIM-domain (JAZ) proteins negatively regulate the biosynthesis of anthocyanins by interacting with bHLH transcription factors. However, it is largely unknown if and how other regulators are involved in this process. In this study, the apple MdJAZ2 protein was characterized in regards to its function in the negative regulation of anthocyanin accumulation and peel coloration. MdJAZ2 was used as a bait to screen a cDNA library using the yeast two-hybrid method. The hypersensitive induced reaction (HIR) proteins, MdHIR2 and MdHIR4, were obtained from this yeast two-hybrid. The ZIM domain of MdJAZ2 and the PHB domain of the MdHIR proteins are necessary for their interactions. The interactions were further verified using an in vitro pull-down assay. Subsequently, immunoblotting assays demonstrated that MdHIR4 enhanced the stability of the MdJAZ2-GUS protein. Finally, a viral vector-based transformation method showed that MdHIR4 inhibited anthocyanin accumulation and fruit coloration in apple by modulating the expression of genes associated with anthocyanin biosynthesis. PMID:28317851

Increased COX-2 expression in epithelial and stromal cells of high mammographic density tissues and in a xenograft model of mammographic density.

PubMed

Chew, G L; Huo, C W; Huang, D; Hill, P; Cawson, J; Frazer, H; Hopper, J L; Haviv, I; Henderson, M A; Britt, K; Thompson, E W

2015-08-01

Mammographic density (MD) adjusted for age and body mass index is one of the strongest known risk factors for breast cancer. Given the high attributable risk of MD for breast cancer, chemoprevention with a safe and available agent that reduces MD and breast cancer risk would be beneficial. Cox-2 has been implicated in MD-related breast cancer risk, and was increased in stromal cells in high MD tissues in one study. Our study assessed differential Cox-2 expression in epithelial and stromal cells in paired samples of high and low MD human breast tissue, and in a validated xenograft biochamber model of MD. We also examined the effects of endocrine treatment upon Cox-2 expression in high and low MD tissues in the MD xenograft model. Paired high and low MD human breast tissue samples were immunostained for Cox-2, then assessed for differential expression and staining intensity in epithelial and stromal cells. High and low MD human breast tissues were separately maintained in biochambers in mice treated with Tamoxifen, oestrogen or placebo implants, then assessed for percentage Cox-2 staining in epithelial and stromal cells. Percentage Cox-2 staining was greater for both epithelial (p = 0.01) and stromal cells (p < 0.0001) of high compared with low MD breast tissues. In high MD biochamber tissues, percentage Cox-2 staining was greater in stromal cells of oestrogen-treated versus placebo-treated tissues (p = 0.05).

Molecular characterization of FLOWERING LOCUS T-like genes of apple (Malus x domestica Borkh.).

PubMed

Kotoda, Nobuhiro; Hayashi, Hidehiro; Suzuki, Motoko; Igarashi, Megumi; Hatsuyama, Yoshimichi; Kidou, Shin-Ichiro; Igasaki, Tomohiro; Nishiguchi, Mitsuru; Yano, Kanako; Shimizu, Tokurou; Takahashi, Sae; Iwanami, Hiroshi; Moriya, Shigeki; Abe, Kazuyuki

2010-04-01

The two FLOWERING LOCUS T (FT)-like genes of apple (Malus x domestica Borkh.), MdFT1 and MdFT2, have been isolated and characterized. MdFT1 and MdFT2 were mapped, respectively, on distinct linkage groups (LGs) with partial homoeology, LG 12 and LG 4. The expression pattern of MdFT1 and MdFT2 differed in that MdFT1 was expressed mainly in apical buds of fruit-bearing shoots in the adult phase, with little expression in the juvenile tissues, whereas MdFT2 was expressed mainly in reproductive organs, including flower buds and young fruit. On the other hand, both genes had the potential to induce early flowering since transgenic Arabidopsis, which ectopically expressed MdFT1 or MdFT2, flowered earlier than wild-type plants. Furthermore, overexpression of MdFT1 conferred precocious flowering in apple, with altered expression of other endogenous genes, such as MdMADS12. These results suggest that MdFT1 could function to promote flowering by altering the expression of those genes and that, at least, other genes may play an important role as well in the regulation of flowering in apple. The long juvenile period of fruit trees prevents early cropping and efficient breeding. Our findings will be useful information to unveil the molecular mechanism of flowering and to develop methods to shorten the juvenile period in various fruit trees, including apple.

The AINTEGUMENTA genes, MdANT1 and MdANT2, are associated with the regulation of cell production during fruit growth in apple (Malus × domestica Borkh.)

PubMed Central

2012-01-01

Background Fruit growth in apple (Malus × domestica Borkh.) is mediated by cell production and expansion. Genes involved in regulating these processes and thereby fruit growth, are not well characterized. We hypothesized that the apple homolog(s) of AINTEGUMENTA (ANT), an APETALA2–repeat containing transcription factor, regulates cell production during fruit growth in apple. Results Two ANT genes, MdANT1 and MdANT2, were isolated from apple and their expression was studied during multiple stages of fruit development. MdANT1 and MdANT2 expression was high during early fruit growth coincident with the period of cell production, rapidly declined during exit from cell production, and remained low during the rest of fruit development. The effects of increase in carbohydrate availability during fruit growth were characterized. Increase in carbohydrate availability enhanced fruit growth largely through an increase in cell production. Expression of MdANT1 and MdANT2 increased sharply by up to around 5-fold in response to an increase in carbohydrate availability. Expression of the ANT genes was compared across two apple genotypes, ‘Gala’ and ‘Golden Delicious Smoothee’ (GS), which differ in the extent of fruit growth, largely due to differences in cell production. In comparison to ‘Gala’, the larger fruit-size genotype, GS, displayed higher levels and a longer duration of MdANT1 and MdANT2 expression. Expression of the ANTs and cell cycle genes in the fruit core and cortex tissues isolated using laser capture microdissection was studied. During early fruit growth, expression of the MdANTs was higher within the cortex, the tissue that constitutes the majority of the fruit. Additionally, MdANT1 and MdANT2 expression was positively correlated with that of A- and B-type CYCLINS, B-type CYCLIN-DEPENDENT-KINASES (CDKBs) and MdDEL1. Conclusions Multiple lines of evidence from this study suggest that MdANT1 and MdANT2 regulate cell production during fruit growth in apple. ANTs may coordinate the expression of cell proliferation genes and thereby affect the competence of cells for cell production during fruit growth. Together, data from this study implicate MdANT1 and MdANT2 in the regulation of fruit growth in apple. PMID:22731507

The AINTEGUMENTA genes, MdANT1 and MdANT2, are associated with the regulation of cell production during fruit growth in apple (Malus × domestica Borkh.).

PubMed

Dash, Madhumita; Malladi, Anish

2012-06-25

Fruit growth in apple (Malus × domestica Borkh.) is mediated by cell production and expansion. Genes involved in regulating these processes and thereby fruit growth, are not well characterized. We hypothesized that the apple homolog(s) of AINTEGUMENTA (ANT), an APETALA2-repeat containing transcription factor, regulates cell production during fruit growth in apple. Two ANT genes, MdANT1 and MdANT2, were isolated from apple and their expression was studied during multiple stages of fruit development. MdANT1 and MdANT2 expression was high during early fruit growth coincident with the period of cell production, rapidly declined during exit from cell production, and remained low during the rest of fruit development. The effects of increase in carbohydrate availability during fruit growth were characterized. Increase in carbohydrate availability enhanced fruit growth largely through an increase in cell production. Expression of MdANT1 and MdANT2 increased sharply by up to around 5-fold in response to an increase in carbohydrate availability. Expression of the ANT genes was compared across two apple genotypes, 'Gala' and 'Golden Delicious Smoothee' (GS), which differ in the extent of fruit growth, largely due to differences in cell production. In comparison to 'Gala', the larger fruit-size genotype, GS, displayed higher levels and a longer duration of MdANT1 and MdANT2 expression. Expression of the ANTs and cell cycle genes in the fruit core and cortex tissues isolated using laser capture microdissection was studied. During early fruit growth, expression of the MdANTs was higher within the cortex, the tissue that constitutes the majority of the fruit. Additionally, MdANT1 and MdANT2 expression was positively correlated with that of A- and B-type CYCLINS, B-type CYCLIN-DEPENDENT-KINASES (CDKBs) and MdDEL1. Multiple lines of evidence from this study suggest that MdANT1 and MdANT2 regulate cell production during fruit growth in apple. ANTs may coordinate the expression of cell proliferation genes and thereby affect the competence of cells for cell production during fruit growth. Together, data from this study implicate MdANT1 and MdANT2 in the regulation of fruit growth in apple.

A Putative Multiple-Demand System in the Macaque Brain.

PubMed

Mitchell, Daniel J; Bell, Andrew H; Buckley, Mark J; Mitchell, Anna S; Sallet, Jerome; Duncan, John

2016-08-17

In humans, cognitively demanding tasks of many types recruit common frontoparietal brain areas. Pervasive activation of this "multiple-demand" (MD) network suggests a core function in supporting goal-oriented behavior. A similar network might therefore be predicted in nonhuman primates that readily perform similar tasks after training. However, an MD network in nonhuman primates has not been described. Single-cell recordings from macaque frontal and parietal cortex show some similar properties to human MD fMRI responses (e.g., adaptive coding of task-relevant information). Invasive recordings, however, come from limited prespecified locations, so they do not delineate a macaque homolog of the MD system and their positioning could benefit from knowledge of where MD foci lie. Challenges of scanning behaving animals mean that few macaque fMRI studies specifically contrast levels of cognitive demand, so we sought to identify a macaque counterpart to the human MD system using fMRI connectivity in 35 rhesus macaques. Putative macaque MD regions, mapped from frontoparietal MD regions defined in humans, were found to be functionally connected under anesthesia. To further refine these regions, an iterative process was used to maximize their connectivity cross-validated across animals. Finally, whole-brain connectivity analyses identified voxels that were robustly connected to MD regions, revealing seven clusters across frontoparietal and insular cortex comparable to human MD regions and one unexpected cluster in the lateral fissure. The proposed macaque MD regions can be used to guide future electrophysiological investigation of MD neural coding and in task-based fMRI to test predictions of similar functional properties to human MD cortex. In humans, a frontoparietal "multiple-demand" (MD) brain network is recruited during a wide range of cognitively demanding tasks. Because this suggests a fundamental function, one might expect a similar network to exist in nonhuman primates, but this remains controversial. Here, we sought to identify a macaque counterpart to the human MD system using fMRI connectivity. Putative macaque MD regions were functionally connected under anesthesia and were further refined by iterative optimization. The result is a network including lateral frontal, dorsomedial frontal, and insular and inferior parietal regions closely similar to the human counterpart. The proposed macaque MD regions can be useful in guiding electrophysiological recordings or in task-based fMRI to test predictions of similar functional properties to human MD cortex. Copyright © 2016 Mitchell et al.

MdHB1 down-regulation activates anthocyanin biosynthesis in the white-fleshed apple cultivar 'Granny Smith'.

PubMed

Jiang, Yonghua; Liu, Cuihua; Yan, Dan; Wen, Xiaohong; Liu, Yanli; Wang, Haojie; Dai, Jieyu; Zhang, Yujie; Liu, Yanfei; Zhou, Bin; Ren, Xiaolin

2017-02-01

Coloration in apple (Malus×domestica) flesh is mainly caused by the accumulation of anthocyanin. Anthocyanin is biosynthesized through the flavonoid pathway and regulated by MYB, bHLH, and WD40 transcription factors (TFs). Here, we report that the HD-Zip I TF MdHB1 was also involved in the regulation of anthocyanin accumulation. MdHB1 silencing caused the accumulation of anthocyanin in 'Granny Smith' flesh, whereas its overexpression reduced the flesh content of anthocyanin in 'Ballerina' (red-fleshed apple). Moreover, flowers of transgenic tobacco (Nicotiana tabacum 'NC89') overexpressing MdHB1 showed a remarkable reduction in pigmentation. Transient promoter activation assays and yeast one-hybrid results indicated that MdHB1 indirectly inhibited expression of the anthocyanin biosynthetic genes encoding dihydroflavonol-4-reductase (DFR) and UDP-glucose:flavonoid 3-O-glycosyltransferase (UFGT). Yeast two-hybrid and bimolecular fluorescence complementation determined that MdHB1 acted as a homodimer and could interact with MYB, bHLH, and WD40 in the cytoplasm, consistent with its cytoplasmic localization by green fluorescent protein fluorescence observations. Together, these results suggest that MdHB1 constrains MdMYB10, MdbHLH3, and MdTTG1 to the cytoplasm, and then represses the transcription of MdDFR and MdUFGT indirectly. When MdHB1 is silenced, these TFs are released to activate the expression of MdDFR and MdUFGT and also anthocyanin biosynthesis, resulting in red flesh in 'Granny Smith'. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Water consumption footprint and land requirements of large-scale alternative diesel and jet fuel production.

PubMed

Staples, Mark D; Olcay, Hakan; Malina, Robert; Trivedi, Parthsarathi; Pearlson, Matthew N; Strzepek, Kenneth; Paltsev, Sergey V; Wollersheim, Christoph; Barrett, Steven R H

2013-01-01

Middle distillate (MD) transportation fuels, including diesel and jet fuel, make up almost 30% of liquid fuel consumption in the United States. Alternative drop-in MD and biodiesel could potentially reduce dependence on crude oil and the greenhouse gas intensity of transportation. However, the water and land resource requirements of these novel fuel production technologies must be better understood. This analysis quantifies the lifecycle green and blue water consumption footprints of producing: MD from conventional crude oil; Fischer-Tropsch MD from natural gas and coal; fermentation and advanced fermentation MD from biomass; and hydroprocessed esters and fatty acids MD and biodiesel from oilseed crops, throughout the contiguous United States. We find that FT MD and alternative MD derived from rainfed biomass have lifecycle blue water consumption footprints of 1.6 to 20.1 Lwater/LMD, comparable to conventional MD, which ranges between 4.1 and 7.4 Lwater/LMD. Alternative MD derived from irrigated biomass has a lifecycle blue water consumption footprint potentially several orders of magnitude larger, between 2.7 and 22 600 Lwater/LMD. Alternative MD derived from biomass has a lifecycle green water consumption footprint between 1.1 and 19 200 Lwater/LMD. Results are disaggregated to characterize the relationship between geo-spatial location and lifecycle water consumption footprint. We also quantify the trade-offs between blue water consumption footprint and areal MD productivity, which ranges from 490 to 4200 LMD/ha, under assumptions of rainfed and irrigated biomass cultivation. Finally, we show that if biomass cultivation for alternative MD is irrigated, the ratio of the increase in areal MD productivity to the increase in blue water consumption footprint is a function of geo-spatial location and feedstock-to-fuel production pathway.

Prostate Cancer Research Training in Health Disparities for Undergraduates (PCaRT)

DTIC Science & Technology

2010-03-01

management Program Mentors Carlton Adams, M.D. LaMonica Stewart, Ph.D. Ben Ogunkua, M.D., Ph.D. Alphonse Pasipanodya, M.D. Jay Fowke, Ph.D., MPH...African-Americans Alphonse Pasipanodya, MD. (Primary Mentor) Flora A. M. Ukoli, MD., MPH. (Principal Investigator) Derrick Beech, M.D. (Co-PI...my goals is to be a successful black woman influencing and touching the lives of all those I come in contact with daily. Alphonse Pasipanodya

The Influence of Perceived Characteristics of Management Development Programs on Employee Outcomes

ERIC Educational Resources Information Center

Ardts, Joost C. A.; van der Velde, Mandy E. G.; Maurer, Todd J.

2010-01-01

Employees' perceptions of Management Development (MD) programs is the topic of this study. The purpose is to examine the influence of three important perceived characteristics of MD programs on relevant MD outcomes. The MD characteristics are: availability of role models, perceived control, and understanding the MD program. Outcomes are:…

Effects of Tamoxifen and oestrogen on histology and radiographic density in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers.

PubMed

Chew, G L; Huo, C W; Huang, D; Blick, T; Hill, P; Cawson, J; Frazer, H; Southey, M C; Hopper, J L; Britt, K; Henderson, M A; Haviv, I; Thompson, E W

2014-11-01

Mammographic density (MD) is a strong risk factor for breast cancer. It is altered by exogenous endocrine treatments, including hormone replacement therapy and Tamoxifen. Such agents also modify breast cancer (BC) risk. However, the biomolecular basis of how systemic endocrine therapy modifies MD and MD-associated BC risk is poorly understood. This study aims to determine whether our xenograft biochamber model can be used to study the effectiveness of therapies aimed at modulating MD, by examine the effects of Tamoxifen and oestrogen on histologic and radiographic changes in high and low MD tissues maintained within the biochamber model. High and low MD human tissues were precisely sampled under radiographic guidance from prophylactic mastectomy fresh specimens of high-risk women, then inserted into separate vascularized murine biochambers. The murine hosts were concurrently implanted with Tamoxifen, oestrogen or placebo pellets, and the high and low MD biochamber tissues maintained in the murine host environment for 3 months, before the high and low MD biochamber tissues were harvested for histologic and radiographic analyses. The radiographic density of high MD tissue maintained in murine biochambers was decreased in Tamoxifen-treated mice compared to oestrogen-treated mice (p = 0.02). Tamoxifen treatment of high MD tissue in SCID mice led to a decrease in stromal (p = 0.009), and an increase in adipose (p = 0.023) percent areas, compared to placebo-treated mice. No histologic or radiographic differences were observed in low MD biochamber tissue with any treatment. High MD biochamber tissues maintained in mice implanted with Tamoxifen, oestrogen or placebo pellets had dynamic and measurable histologic compositional and radiographic changes. This further validates the dynamic nature of the MD xenograft model, and suggests the biochamber model may be useful for assessing the underlying molecular pathways of Tamoxifen-reduced MD, and in testing of other pharmacologic interventions in a preclinical model of high MD.

Null mutation of the MdACS3 gene, coding for a ripening-specific 1-aminocyclopropane-1-carboxylate synthase, leads to long shelf life in apple fruit.

PubMed

Wang, Aide; Yamakake, Junko; Kudo, Hisayuki; Wakasa, Yuhya; Hatsuyama, Yoshimichi; Igarashi, Megumi; Kasai, Atsushi; Li, Tianzhong; Harada, Takeo

2009-09-01

Expression of MdACS1, coding for 1-aminocyclopropane-1-carboxylate synthase (ACS), parallels the level of ethylene production in ripening apple (Malus domestica) fruit. Here we show that expression of another ripening-specific ACS gene (MdACS3) precedes the initiation of MdACS1 expression by approximately 3 weeks; MdACS3 expression then gradually decreases as MdACS1 expression increases. Because MdACS3 expression continues in ripening fruit treated with 1-methylcyclopropene, its transcription appears to be regulated by a negative feedback mechanism. Three genes in the MdACS3 family (a, b, and c) were isolated from a genomic library, but two of them (MdACS3b and MdACS3c) possess a 333-bp transposon-like insertion in their 5' flanking region that may prevent transcription of these genes during ripening. A single nucleotide polymorphism in the coding region of MdACS3a results in an amino acid substitution (glycine-289 --> valine) in the active site that inactivates the enzyme. Furthermore, another null allele of MdACS3a, Mdacs3a, showing no ability to be transcribed, was found by DNA sequencing. Apple cultivars homozygous or heterozygous for both null allelotypes showed no or very low expression of ripening-related genes and maintained fruit firmness. These results suggest that MdACS3a plays a crucial role in regulation of fruit ripening in apple, and is a possible determinant of ethylene production and shelf life in apple fruit.

Chronic intraventricular administration of lysergic acid diethylamide (LSD) affects the sensitivity of cortical cells to monocular deprivation.

PubMed

McCall, M A; Tieman, D G; Hirsch, H V

1982-11-04

In kittens, but not in adult cats, depriving one eye of pattern vision by suturing the lids shut (monocular deprivation or MD) for one week reduces the proportion of binocular units in the visual cortex. A sensitivity of cortical units in adult cats to MD can be produced by infusing exogenous monoamines into the visual cortex. Since LSD interacts with monoamines, we have examined the effects of chronic administration of LSD on the sensitivity to MD for cortical cells in adult cats. Cats were assigned randomly to one of four conditions: MD/LSD, MD/No-LSD, No-MD/LSD, No-MD/No-LSD. An osmotic minipump delivered either LSD or the vehicle solution alone during a one-week period of MD. The animals showed no obvious anomalies during the administration of the drug. After one week the response properties of single units in area 17 of the visual cortex were studied without knowledge of the contents of the individual minipumps. With the exception of ocular dominance, the response properties of units recorded in all animals did not differ from normal. In the control animals (MD/No-LSD, No-MD/LSD, No-MD/No-LSD) the average proportion of binocular cells was 78%; similar to that observed for normal adult cats. However, in the experimental animals, which received LSD during the period of MD, only 52% of the cells were binocular. Our results suggest that chronic intraventricular administration of LSD affects either directly or indirectly the sensitivity of cortical neurons to MD.

Proposal and Testing of a Methodology for Evaluating an Occupational Health Program at a U.S. Army Installation

DTIC Science & Technology

1983-08-01

the literature for ten of the thirteen peptic ulcer diagnostic criteria most often cited in predeveloped listings compiled by various professional...Dershewitz, M.D., Richard A. Gross, M.D., and John W. Williamson, M.D., "Validating Audit Criteria: An Analytic Approach Illustrated by Peptic Ulcer ...A., M.D.; Gross, Richard A., M.D.; and Williamson, John W., M.D., "Validating Audit Criteria: An Analytic Approach Illustrated by Peptic Ulcer Disease

[Evaluation of three methods for forensic diatom test].

PubMed

Wang, Yuzhong; Zhao, Jian; Li, Peng; Hu, Sunlin; Wang, Huipin; Wang, Huijun; Liu, Chao

2015-03-01

To compare the efficacy of three methods for forensic diatom test, namely strong acid digestion-centrifuge enrichment-light microscopy (SD-CE-LM), microwave digestion-membrane filtration-automated scanning electron microscopy (MD-ME-SEM), and microwave digestion-membrane filtration-light microscopy (MD-MF-LM). Sixty samples were randomly divided into 3 groups for diatom test using three methods, and the sample preparation time, degree of digestion and recovery rate of diatoms were compared. The sample preparation time was the shortest with MD-MF-LM and the longest with SD-CE-LM (P<0.05). MD-ME-SEM and MD-MF-LM allowed more thorough tissue digestion than SD-CE-LM. MD-ME-SEM resulted in the highest total recovery rate of diatom, followed by MD-MF-LM and then by SD-CE-LM (P<0.05); the recover rate of different diatom species was the highest with MD-ME-SEM, followed by MD-MF-LM and SD-CE-LM (P<0.05). SD-CE-LM has a low recovery rate of diatoms especially for those with lengths shorter than 40 µm or densities less than 1/5. With a high recovery rate and accuracy in diatom test, MD-ME-SEM is suitable for diagnosis of suspected drowning cases. MD-MF-LM is highly efficient, sensitive and convenient for forensic diatom test.

SVP-like MADS Box Genes Control Dormancy and Budbreak in Apple

PubMed Central

Wu, Rongmei; Tomes, Sumathi; Karunairetnam, Sakuntala; Tustin, Stuart D.; Hellens, Roger P.; Allan, Andrew C.; Macknight, Richard C.; Varkonyi-Gasic, Erika

2017-01-01

The annual growth cycle of trees is the result of seasonal cues. The onset of winter triggers an endodormant state preventing bud growth and, once a chilling requirement is satisfied, these buds enter an ecodormant state and resume growing. MADS-box genes with similarity to Arabidopsis SHORT VEGETATIVE PHASE (SVP) [the SVP-like and DORMANCY ASSOCIATED MADS-BOX (DAM) genes] have been implicated in regulating flowering and growth-dormancy cycles in perennials. Here, we identified and characterized three DAM-like (MdDAMs) and two SHORT VEGETATIVE PHASE-like (MdSVPs) genes from apple (Malus × domestica ‘Royal Gala’). The expression of MdDAMa and MdDAMc indicated they may play a role in triggering autumn growth cessation. In contrast, the expression of MdDAMb, MdSVPa and MdSVPb suggested a role in maintaining bud dormancy. Consistent with this, ectopic expression of MdDAMb and MdSVPa in ‘Royal Gala’ apple plants resulted in delayed budbreak and architecture change due to constrained lateral shoot outgrowth, but normal flower and fruit development. The association of MdSVPa and MdSVPb expression with floral bud development in the low fruiting ‘Off’ trees of a biennial bearing cultivar ‘Sciros’ suggested the SVP genes might also play a role in floral meristem identity. PMID:28421103

ANA (Antinuclear Antibody Test)

MedlinePlus

... findarticles.com . Kavanaugh A, Tomar R, Reveille J, Solomon DH, Homburger HA. Guidelines for clinical use of ... Russell Tomar, MD, John Reveille, MD, Daniel H. Solomon, MD, MPH, and Henry A. Homburger, MD. Guidelines ...

Dynamic changes in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers during various murine peripartum states and over time.

PubMed

Chew, G L; Huang, D; Huo, C W; Blick, T; Hill, P; Cawson, J; Frazer, H; Southey, M D; Hopper, J L; Henderson, M A; Haviv, I; Thompson, E W

2013-07-01

Mammographic density (MD) is a strong heritable risk factor for breast cancer, and may decrease with increasing parity. However, the biomolecular basis for MD-associated breast cancer remains unclear, and systemic hormonal effects on MD-associated risk is poorly understood. This study assessed the effect of murine peripartum states on high and low MD tissue maintained in a xenograft model of human MD. Method High and low MD human breast tissues were precisely sampled under radiographic guidance from prophylactic mastectomy specimens of women. The high and low MD tissues were maintained in separate vascularised biochambers in nulliparous or pregnant SCID mice for 4 weeks, or mice undergoing postpartum involution or lactation for three additional weeks. High and low MD biochamber material was harvested for histologic and radiographic comparisons during various murine peripartum states. High and low MD biochamber tissues in nulliparous mice were harvested at different timepoints for histologic and radiographic comparisons. Results High MD biochamber tissues had decreased stromal (p = 0.0027), increased adipose (p = 0.0003) and a trend to increased glandular tissue areas (p = 0.076) after murine postpartum involution. Stromal areas decreased (p = 0.042), while glandular (p = 0.001) and adipose areas (p = 0.009) increased in high MD biochamber tissues during lactation. A difference in radiographic density was observed in high (p = 0.0021) or low MD biochamber tissues (p = 0.004) between nulliparous, pregnant and involution groups. No differences in tissue composition were observed in high or low MD biochamber tissues maintained for different durations, although radiographic density increased over time. Conclusion High MD biochamber tissues had measurable histologic changes after postpartum involution or lactation. Alterations in radiographic density occurred in biochamber tissues between different peripartum states and over time. These findings demonstrate the dynamic nature of the human MD xenograft model, providing a platform for studying the biomolecular basis of MD-associated cancer risk.

Adsorption mechanism of physiologically active L-phenylalanine phosphonodipeptide analogues: Comparison of colloidal silver and macroscopic silver substrates

NASA Astrophysics Data System (ADS)

Podstawka, E.; Kudelski, A.; Proniewicz, L. M.

2007-11-01

Here we present SERS spectra of several L-phenylalanine (Phe) phosphonodipeptides, i.e., L-Phe- L-Ala-PO 3H 2 ( MD1), L-Phe- L-Va L-PO 3H 2 ( MD2), L-Phe-β-Ala-CH(OH)-PO 3H 2 ( MD3), L-Phe- L-Ala-CH(OH)-PO 3H 2 ( MD4), L-Ala-(3,4-dimethoxy)- L-Phe-PO 3H 2 ( MD5), and L-Ala-(3,4-dimethoxy)-(des-CH 2)- L-Phe-PO 3H 2 ( MD6), immobilized on electrochemically roughened silver electrodes. These spectra are analyzed by theoretical calculations using density functional theory (DFT) at the B3LYP level with 6-31++G∗∗ basis set. In addition, these spectra are compared with SERS spectra of these species adsorbed on a colloidal silver surface. We showed that on the macroscopic silver substrate, the Phe aromatic ring of MD3 and MD4 is oriented vertically, while for MD1 it almost "stands up" on this surface. In the other three cases, the Phe ring adopts a tilted orientation in regard to the substrate. We also find that the phosphonate (-PO32-), methyl/methane, or dimethoxy groups of MD1, MD2, MD3, MD5, and MD6 are involved in the interaction of these phosphonodipeptides with the electrochemically roughened surface. This phenomenon is clearly seen for -CH 2-/-CH 3/-OCH 3 moieties as well as for the PO32- group that adsorbs on the macroscopic silver substrates mainly via the P dbnd O fragment. We also showed that MD4 binds to the macroscopic silver substrate through the hydroxyl, amine, and phosphonate groups, while the methylene/methane moieties are remote from this surface. We found that studied phosphonodipeptides often adsorb differently on the macroscopic silver substrate and on the colloidal silver nanoparticles. For example, MD1 adopts an almost vertical orientation on the electrochemically roughened silver substrate and is tilted or close to flat on the silver nanoparticles.

75 FR 31835 - Environmental Impact Statement: Calvert and St. Mary's Counties, MD

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-04

...: Calvert and St. Mary's Counties, MD AGENCY: Federal Highway Administration (FHWA), DOT. ACTION: Notice of... project in Calvert and St. Mary's Counties, Maryland (Federal Register Vol. 72, No. 203; FR Doc. 07-5190... replacement of MD 4 from MD 2 to MD 235 in Calvert and St. Mary's Counties, a distance of approximately 4.1...

Evaluation and Management of Patients with Inhalation Injury

DTIC Science & Technology

1990-12-01

PRUITT, Jr., M.D., WILLIAM G. CIOFFI, M.D., TAKESHI SHIMAZU, M.D. HISASHI IKEUCHI, M.D., AND ARTHUR D. MASON, Jr., M.D. D T CO ELECTE" Inhalation...215, 1988. Do you think that there is some common pathway here 22. Kimura , R., Traber, L., Herndon, D., et al: Ibuprofen reduces the where there is

Registration of cotton germplasm line md 10-5

USDA-ARS?s Scientific Manuscript database

MD 10-5 (Reg. No. ______, PI 675077) is a noncommercial breeding line of cotton (Gossypium hirsutum L.) released by the USDA-ARS at Stoneville, MS in 2015. MD 10-5 was selected in F4 progenies from a cross between MD 15 (PI 642769) and JJ 1145ne. MD 10-5 has a desirable combination between lint yi...

Parallel cascade selection molecular dynamics for efficient conformational sampling and free energy calculation of proteins

NASA Astrophysics Data System (ADS)

Kitao, Akio; Harada, Ryuhei; Nishihara, Yasutaka; Tran, Duy Phuoc

2016-12-01

Parallel Cascade Selection Molecular Dynamics (PaCS-MD) was proposed as an efficient conformational sampling method to investigate conformational transition pathway of proteins. In PaCS-MD, cycles of (i) selection of initial structures for multiple independent MD simulations and (ii) conformational sampling by independent MD simulations are repeated until the convergence of the sampling. The selection is conducted so that protein conformation gradually approaches a target. The selection of snapshots is a key to enhance conformational changes by increasing the probability of rare event occurrence. Since the procedure of PaCS-MD is simple, no modification of MD programs is required; the selections of initial structures and the restart of the next cycle in the MD simulations can be handled with relatively simple scripts with straightforward implementation. Trajectories generated by PaCS-MD were further analyzed by the Markov state model (MSM), which enables calculation of free energy landscape. The combination of PaCS-MD and MSM is reported in this work.

ProtoMD: A prototyping toolkit for multiscale molecular dynamics

NASA Astrophysics Data System (ADS)

Somogyi, Endre; Mansour, Andrew Abi; Ortoleva, Peter J.

2016-05-01

ProtoMD is a toolkit that facilitates the development of algorithms for multiscale molecular dynamics (MD) simulations. It is designed for multiscale methods which capture the dynamic transfer of information across multiple spatial scales, such as the atomic to the mesoscopic scale, via coevolving microscopic and coarse-grained (CG) variables. ProtoMD can be also be used to calibrate parameters needed in traditional CG-MD methods. The toolkit integrates 'GROMACS wrapper' to initiate MD simulations, and 'MDAnalysis' to analyze and manipulate trajectory files. It facilitates experimentation with a spectrum of coarse-grained variables, prototyping rare events (such as chemical reactions), or simulating nanocharacterization experiments such as terahertz spectroscopy, AFM, nanopore, and time-of-flight mass spectroscopy. ProtoMD is written in python and is freely available under the GNU General Public License from github.com/CTCNano/proto_md.

Volumetrics relate to the development of depression after traumatic brain injury.

PubMed

Maller, Jerome J; Thomson, Richard H S; Pannek, Kerstin; Bailey, Neil; Lewis, Philip M; Fitzgerald, Paul B

2014-09-01

Previous research suggests that many people who sustain a traumatic brain injury (TBI), even of the mild form, will develop major depression (MD). We previously reported white matter integrity differences between those who did and did not develop MD after mild TBI. In this current paper, we aimed to investigate whether there were also volumetric differences between these groups, as suggested by previous volumetric studies in mild TBI populations. A sample of TBI-with-MD subjects (N=14), TBI-without-MD subjects (N=12), MD-without-TBI (N=26) and control subjects (no TBI or MD, N=23), received structural MRI brain scans. T1-weighted data were analysed using the Freesurfer software package which produces automated volumetric results. The findings of this study indicate that (1) TBI patients who develop MD have reduced volume in temporal, parietal and lingual regions compared to TBI patients who do not develop MD, and (2) MD patients with a history of TBI have decreased volume in the temporal region compared to those who had MD but without a history of TBI. We also found that more severe MD in those with TBI-with-MD significantly correlated with reduced volume in anterior cingulate, temporal lobe and insula. These findings suggest that volumetric reduction to specific regions, including parietal, temporal and occipital lobes, after a mild TBI may underlie the susceptibility of these patients developing major depression, in addition to altered white matter integrity. Copyright © 2014 Elsevier B.V. All rights reserved.

The medial dorsal thalamic nucleus and the medial prefrontal cortex of the rat function together to support associative recognition and recency but not item recognition.

PubMed

Cross, Laura; Brown, Malcolm W; Aggleton, John P; Warburton, E Clea

2012-12-21

In humans recognition memory deficits, a typical feature of diencephalic amnesia, have been tentatively linked to mediodorsal thalamic nucleus (MD) damage. Animal studies have occasionally investigated the role of the MD in single-item recognition, but have not systematically analyzed its involvement in other recognition memory processes. In Experiment 1 rats with bilateral excitotoxic lesions in the MD or the medial prefrontal cortex (mPFC) were tested in tasks that assessed single-item recognition (novel object preference), associative recognition memory (object-in-place), and recency discrimination (recency memory task). Experiment 2 examined the functional importance of the interactions between the MD and mPFC using disconnection techniques. Unilateral excitotoxic lesions were placed in both the MD and the mPFC in either the same (MD + mPFC Ipsi) or opposite hemispheres (MD + mPFC Contra group). Bilateral lesions in the MD or mPFC impaired object-in-place and recency memory tasks, but had no effect on novel object preference. In Experiment 2 the MD + mPFC Contra group was significantly impaired in the object-in-place and recency memory tasks compared with the MD + mPFC Ipsi group, but novel object preference was intact. Thus, connections between the MD and mPFC are critical for recognition memory when the discriminations involve associative or recency information. However, the rodent MD is not necessary for single-item recognition memory.

Physician self-disclosure in primary care visits: enough about you, what about me?

PubMed

McDaniel, Susan H; Beckman, Howard B; Morse, Diane S; Silberman, Jordan; Seaburn, David B; Epstein, Ronald M

2007-06-25

The value of physician self-disclosure (MD-SD) in creating successful patient-physician partnerships has not been demonstrated. To describe antecedents, delivery, and effects of MD-SD in primary care visits, we conducted a descriptive study using sequence analysis of transcripts of 113 unannounced, undetected, standardized patient visits to primary care physicians. Our main outcome measures were the number of MD-SDs per visit; number of visits with MD-SDs; word count; antecedents, timing, and effect of MD-SD on subsequent physician and patient communication; content and focus of MD-SD. The MD-SDs included discussion of personal emotions and experiences, families and/or relationships, professional descriptions, and personal experiences with the patient's diagnosis. Seventy-three MD-SDs were identified in 38 (34%) of 113 visits. Ten MD-SDs (14%) were a response to a patient question. Forty-four (60%) followed patient symptoms, family, or feelings; 29 (40%) were unrelated. Only 29 encounters (21%) returned to the patient topic preceding the disclosure. Most MD-SDs (n=62; 85%) were not considered useful to the patient by the research team. Eight MD-SDs (11%) were coded as disruptive. Practicing primary care physicians disclosed information about themselves or their families in 34% of new visits with unannounced, undetected, standardized patients. There was no evidence of positive effect of MD-SDs; some appeared disruptive. Primary care physicians should consider when self-disclosing whether other behaviors such as empathy might accomplish their goals more effectively.

The relationship between better-eye and integrated visual field mean deviation and visual disability.

PubMed

Arora, Karun S; Boland, Michael V; Friedman, David S; Jefferys, Joan L; West, Sheila K; Ramulu, Pradeep Y

2013-12-01

To determine the extent of difference between better-eye visual field (VF) mean deviation (MD) and integrated VF (IVF) MD among Salisbury Eye Evaluation (SEE) subjects and a larger group of glaucoma clinic subjects and to assess how those measures relate to objective and subjective measures of ability/performance in SEE subjects. Retrospective analysis of population- and clinic-based samples of adults. A total of 490 SEE and 7053 glaucoma clinic subjects with VF loss (MD ≤-3 decibels [dB] in at least 1 eye). Visual field testing was performed in each eye, and IVF MD was calculated. Differences between better-eye and IVF MD were calculated for SEE and clinic-based subjects. In SEE subjects with VF loss, models were constructed to compare the relative impact of better-eye and IVF MD on driving habits, mobility, self-reported vision-related function, and reading speed. Difference between better-eye and IVF MD and relationship of better-eye and IVF MD with performance measures. The median difference between better-eye and IVF MD was 0.41 dB (interquartile range [IQR], -0.21 to 1.04 dB) and 0.72 dB (IQR, 0.04-1.45 dB) for SEE subjects and clinic-based patients with glaucoma, respectively, with differences of ≥ 2 dB between the 2 MDs observed in 9% and 18% of the groups, respectively. Among SEE subjects with VF loss, both MDs demonstrated similar associations with multiple ability and performance metrics as judged by the presence/absence of a statistically significant association between the MD and the metric, the magnitude of observed associations (odds ratios, rate ratios, or regression coefficients associated with 5-dB decrements in MD), and the extent of variability in the metric explained by the model (R(2)). Similar associations of similar magnitude also were noted for the subgroup of subjects with glaucoma and subjects in whom better-eye and IVF MD differed by ≥ 2 dB. The IVF MD rarely differs from better-eye MD, and similar associations between VF loss and visual disability are obtained using either MD. Unlike better-eye MD, IVF measurements require extra software/calculation. As such, information from studies using better-eye MD can be more easily integrated into clinical decision-making, making better-eye MD a robust and meaningful method for reporting VF loss severity. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Replica Exchange Gaussian Accelerated Molecular Dynamics: Improved Enhanced Sampling and Free Energy Calculation.

PubMed

Huang, Yu-Ming M; McCammon, J Andrew; Miao, Yinglong

2018-04-10

Through adding a harmonic boost potential to smooth the system potential energy surface, Gaussian accelerated molecular dynamics (GaMD) provides enhanced sampling and free energy calculation of biomolecules without the need of predefined reaction coordinates. This work continues to improve the acceleration power and energy reweighting of the GaMD by combining the GaMD with replica exchange algorithms. Two versions of replica exchange GaMD (rex-GaMD) are presented: force constant rex-GaMD and threshold energy rex-GaMD. During simulations of force constant rex-GaMD, the boost potential can be exchanged between replicas of different harmonic force constants with fixed threshold energy. However, the algorithm of threshold energy rex-GaMD tends to switch the threshold energy between lower and upper bounds for generating different levels of boost potential. Testing simulations on three model systems, including the alanine dipeptide, chignolin, and HIV protease, demonstrate that through continuous exchanges of the boost potential, the rex-GaMD simulations not only enhance the conformational transitions of the systems but also narrow down the distribution width of the applied boost potential for accurate energetic reweighting to recover biomolecular free energy profiles.

A CIPK protein kinase targets sucrose transporter MdSUT2.2 at Ser254 for phosphorylation to enhance salt tolerance.

PubMed

Ma, Qi-Jun; Sun, Mei-Hong; Kang, Hui; Lu, Jing; You, Chun-Xiang; Hao, Yu-Jin

2018-05-23

Soil salinity is one of the major abiotic stressors that negatively affect crop growth and yield. Salt stress can regulate antioxidants and the accumulation of osmoprotectants. In the study, a sucrose transporter MdSUT2.2 was identified in apple. Overexpression of MdSUT2.2 gene increased salt tolerance in the transgenic apple, compared with the WT control 'Gala'. In addition, it was found that protein MdSUT2.2 was phosphorylated at Ser 254 site in response to salt. A DUAL membrane yeast hybridization system through an apple cDNA library demonstrated that a protein kinase MdCIPK13 interacted with MdSUT2.2. A series of transgenic analysis in apple calli showed that MdCIPK13 was required for the salt-induced phosphorylation of MdSUT2.2 protein and enhanced its stability and transport activity. Finally, it was found that MdCIPK13 improved salt resistance in an MdSUT2.2-dependent manner. These findings had enriched our understanding of the molecular mechanisms underlying abiotic stress. This article is protected by copyright. All rights reserved.

Rapid exploration of configuration space with diffusion-map-directed molecular dynamics.

PubMed

Zheng, Wenwei; Rohrdanz, Mary A; Clementi, Cecilia

2013-10-24

The gap between the time scale of interesting behavior in macromolecular systems and that which our computational resources can afford often limits molecular dynamics (MD) from understanding experimental results and predicting what is inaccessible in experiments. In this paper, we introduce a new sampling scheme, named diffusion-map-directed MD (DM-d-MD), to rapidly explore molecular configuration space. The method uses a diffusion map to guide MD on the fly. DM-d-MD can be combined with other methods to reconstruct the equilibrium free energy, and here, we used umbrella sampling as an example. We present results from two systems: alanine dipeptide and alanine-12. In both systems, we gain tremendous speedup with respect to standard MD both in exploring the configuration space and reconstructing the equilibrium distribution. In particular, we obtain 3 orders of magnitude of speedup over standard MD in the exploration of the configurational space of alanine-12 at 300 K with DM-d-MD. The method is reaction coordinate free and minimally dependent on a priori knowledge of the system. We expect wide applications of DM-d-MD to other macromolecular systems in which equilibrium sampling is not affordable by standard MD.

Rapid Exploration of Configuration Space with Diffusion Map-directed-Molecular Dynamics

PubMed Central

Zheng, Wenwei; Rohrdanz, Mary A.; Clementi, Cecilia

2013-01-01

The gap between the timescale of interesting behavior in macromolecular systems and that which our computational resources can afford oftentimes limits Molecular Dynamics (MD) from understanding experimental results and predicting what is inaccessible in experiments. In this paper, we introduce a new sampling scheme, named Diffusion Map-directed-MD (DM-d-MD), to rapidly explore molecular configuration space. The method uses diffusion map to guide MD on the fly. DM-d-MD can be combined with other methods to reconstruct the equilibrium free energy, and here we used umbrella sampling as an example. We present results from two systems: alanine dipeptide and alanine-12. In both systems we gain tremendous speedup with respect to standard MD both in exploring the configuration space and reconstructing the equilibrium distribution. In particular, we obtain 3 orders of magnitude of speedup over standard MD in the exploration of the configurational space of alanine-12 at 300K with DM-d-MD. The method is reaction coordinate free and minimally dependent on a priori knowledge of the system. We expect wide applications of DM-d-MD to other macromolecular systems in which equilibrium sampling is not affordable by standard MD. PMID:23865517

Use of FGF-21 as a Biomarker of Mitochondrial Disease in Clinical Practice.

PubMed

Morovat, Alireza; Weerasinghe, Gayani; Nesbitt, Victoria; Hofer, Monika; Agnew, Thomas; Quaghebeur, Geralrine; Sergeant, Kate; Fratter, Carl; Guha, Nishan; Mirzazadeh, Mehdi; Poulton, Joanna

2017-08-21

Recent work has suggested that fibroblast growth factor-21 (FGF-21) is a useful biomarker of mitochondrial disease (MD). We routinely measured FGF-21 levels on patients who were investigated at our centre for MD and evaluated its diagnostic performance based on detailed genetic and other laboratory findings. Patients' FGF-21 results were assessed by the use of age-adjusted z -scores based on normalised FGF-21 values from a healthy population. One hundred and fifty five patients were investigated. One hundred and four of these patients had molecular evidence for MD, 27 were deemed to have disorders other than MD (non-MD), and 24 had possible MD. Patients with defects in mitochondrial DNA (mtDNA) maintenance ( n = 32) and mtDNA rearrangements ( n = 17) had the highest median FGF-21 among the MD group. Other MD patients harbouring mtDNA point mutations ( n = 40) or mutations in other autosomal genes ( n = 7) and those with partially characterised MD had lower FGF-21 levels. The area under the receiver operating characteristic curve for distinguishing MD from non-MD patients was 0.69. No correlation between FGF-21 and creatinine, creatine kinase, or cardio-skeletal myopathy score was found. FGF-21 was significantly associated with plasma lactate and ocular myopathy. Although FGF-21 was found to have a low sensitivity for detecting MD, at a z -score of 2.8, its specificity was above 90%. We suggest that a high serum concentration of FGF-21 would be clinically useful in MD, especially in adult patients with chronic progressive external ophthalmoplegia, and may enable bypassing muscle biopsy and directly opting for genetic analysis. Availability of its assay has thus modified our diagnostic pathway.

Use of FGF-21 as a Biomarker of Mitochondrial Disease in Clinical Practice

PubMed Central

Weerasinghe, Gayani; Nesbitt, Victoria; Hofer, Monika; Agnew, Thomas; Quaghebeur, Geralrine; Sergeant, Kate; Guha, Nishan; Mirzazadeh, Mehdi; Poulton, Joanna

2017-01-01

Recent work has suggested that fibroblast growth factor-21 (FGF-21) is a useful biomarker of mitochondrial disease (MD). We routinely measured FGF-21 levels on patients who were investigated at our centre for MD and evaluated its diagnostic performance based on detailed genetic and other laboratory findings. Patients’ FGF-21 results were assessed by the use of age-adjusted z-scores based on normalised FGF-21 values from a healthy population. One hundred and fifty five patients were investigated. One hundred and four of these patients had molecular evidence for MD, 27 were deemed to have disorders other than MD (non-MD), and 24 had possible MD. Patients with defects in mitochondrial DNA (mtDNA) maintenance (n = 32) and mtDNA rearrangements (n = 17) had the highest median FGF-21 among the MD group. Other MD patients harbouring mtDNA point mutations (n = 40) or mutations in other autosomal genes (n = 7) and those with partially characterised MD had lower FGF-21 levels. The area under the receiver operating characteristic curve for distinguishing MD from non-MD patients was 0.69. No correlation between FGF-21 and creatinine, creatine kinase, or cardio-skeletal myopathy score was found. FGF-21 was significantly associated with plasma lactate and ocular myopathy. Although FGF-21 was found to have a low sensitivity for detecting MD, at a z-score of 2.8, its specificity was above 90%. We suggest that a high serum concentration of FGF-21 would be clinically useful in MD, especially in adult patients with chronic progressive external ophthalmoplegia, and may enable bypassing muscle biopsy and directly opting for genetic analysis. Availability of its assay has thus modified our diagnostic pathway. PMID:28825656

Molecular cloning and functional analysis of a blue light receptor gene MdCRY2 from apple (Malus domestica).

PubMed

Li, Yuan-Yuan; Mao, Ke; Zhao, Cheng; Zhao, Xian-Yan; Zhang, Rui-Fen; Zhang, Hua-Lei; Shu, Huai-Rui; Hao, Yu-Jin

2013-04-01

MdCRY2 was isolated from apple fruit skin, and its function was analyzed in MdCRY2 transgenic Arabidopsis. The interaction between MdCRY2 and AtCOP1 was found by yeast two-hybrid and BiFC assays. Cryptochromes are blue/ultraviolet-A (UV-A) light receptors involved in regulating various aspects of plant growth and development. Investigations of the structure and functions of cryptochromes in plants have largely focused on Arabidopsis (Arabidopsis thaliana), tomato (Solanum lycopersicum), pea (Pisum sativum), and rice (Oryza sativa). However, no data on the function of CRY2 are available in woody plants. In this study, we isolated a cryptochrome gene, MdCRY2, from apple (Malus domestica). The deduced amino acid sequences of MdCRY2 contain the conserved N-terminal photolyase-related domain and the flavin adenine dinucleotide (FAD) binding domain, as well as the C-terminal DQXVP-acidic-STAES (DAS) domain. Relationship analysis indicates that MdCRY2 shows the highest similarity to the strawberry FvCRY protein. The expression of MdCRY2 is induced by blue/UV-A light, which represents a 48-h circadian rhythm. To investigate the function of MdCRY2, we overexpressed the MdCRY2 gene in a cry2 mutant and wild type (WT) Arabidopsis, assessed the phenotypes of the resulting transgenic plants, and found that MdCRY2 functions to regulate hypocotyl elongation, root growth, flower initiation, and anthocyanin accumulation. Furthermore, we examined the interaction between MdCRY2 and AtCOP1 using a yeast two-hybrid assay and a bimolecular fluorescence complementation assay. These data provide functional evidence for a role of blue/UV-A light-induced MdCRY2 in controlling photomorphogenesis in apple.

Gaussian Accelerated Molecular Dynamics in NAMD

PubMed Central

2016-01-01

Gaussian accelerated molecular dynamics (GaMD) is a recently developed enhanced sampling technique that provides efficient free energy calculations of biomolecules. Like the previous accelerated molecular dynamics (aMD), GaMD allows for “unconstrained” enhanced sampling without the need to set predefined collective variables and so is useful for studying complex biomolecular conformational changes such as protein folding and ligand binding. Furthermore, because the boost potential is constructed using a harmonic function that follows Gaussian distribution in GaMD, cumulant expansion to the second order can be applied to recover the original free energy profiles of proteins and other large biomolecules, which solves a long-standing energetic reweighting problem of the previous aMD method. Taken together, GaMD offers major advantages for both unconstrained enhanced sampling and free energy calculations of large biomolecules. Here, we have implemented GaMD in the NAMD package on top of the existing aMD feature and validated it on three model systems: alanine dipeptide, the chignolin fast-folding protein, and the M3 muscarinic G protein-coupled receptor (GPCR). For alanine dipeptide, while conventional molecular dynamics (cMD) simulations performed for 30 ns are poorly converged, GaMD simulations of the same length yield free energy profiles that agree quantitatively with those of 1000 ns cMD simulation. Further GaMD simulations have captured folding of the chignolin and binding of the acetylcholine (ACh) endogenous agonist to the M3 muscarinic receptor. The reweighted free energy profiles are used to characterize the protein folding and ligand binding pathways quantitatively. GaMD implemented in the scalable NAMD is widely applicable to enhanced sampling and free energy calculations of large biomolecules. PMID:28034310

Null Mutation of the MdACS3 Gene, Coding for a Ripening-Specific 1-Aminocyclopropane-1-Carboxylate Synthase, Leads to Long Shelf Life in Apple Fruit1[W][OA

PubMed Central

Wang, Aide; Yamakake, Junko; Kudo, Hisayuki; Wakasa, Yuhya; Hatsuyama, Yoshimichi; Igarashi, Megumi; Kasai, Atsushi; Li, Tianzhong; Harada, Takeo

2009-01-01

Expression of MdACS1, coding for 1-aminocyclopropane-1-carboxylate synthase (ACS), parallels the level of ethylene production in ripening apple (Malus domestica) fruit. Here we show that expression of another ripening-specific ACS gene (MdACS3) precedes the initiation of MdACS1 expression by approximately 3 weeks; MdACS3 expression then gradually decreases as MdACS1 expression increases. Because MdACS3 expression continues in ripening fruit treated with 1-methylcyclopropene, its transcription appears to be regulated by a negative feedback mechanism. Three genes in the MdACS3 family (a, b, and c) were isolated from a genomic library, but two of them (MdACS3b and MdACS3c) possess a 333-bp transposon-like insertion in their 5′ flanking region that may prevent transcription of these genes during ripening. A single nucleotide polymorphism in the coding region of MdACS3a results in an amino acid substitution (glycine-289 → valine) in the active site that inactivates the enzyme. Furthermore, another null allele of MdACS3a, Mdacs3a, showing no ability to be transcribed, was found by DNA sequencing. Apple cultivars homozygous or heterozygous for both null allelotypes showed no or very low expression of ripening-related genes and maintained fruit firmness. These results suggest that MdACS3a plays a crucial role in regulation of fruit ripening in apple, and is a possible determinant of ethylene production and shelf life in apple fruit. PMID:19587104

Trends in MD/PhD Graduates Entering Psychiatry: Assessing the Physician-Scientist Pipeline.

PubMed

Arbuckle, Melissa R; Luo, Sean X; Pincus, Harold Alan; Gordon, Joshua A; Chung, Joyce Y; Chavez, Mark; Oquendo, Maria A

2018-06-01

The goal of this study was to identify trends in MD/PhD graduates entering psychiatry, to compare these trends with other specialties, and to review strategies for enhancing the physician-scientist pipeline. Data on 226,588 medical students graduating from Liaison Committee on Medical Education accredited programs between 1999 and 2012 (6626 MD/PhDs) were used to evaluate the number, percentage, and proportion of MD/PhDs entering psychiatry in comparison with other specialties (neurology, neurosurgery, internal medicine, family medicine, and radiation oncology). Linear regression and multiple linear regression determined whether these values increased over time and varied by sex. Over 14 years, an average of 18 MD/PhDs (range 13-29) enrolled in psychiatry each year. The number of MD/PhDs going into psychiatry significantly increased, although these gains were modest (less than one additional MD/PhD per year). The proportion of students entering psychiatry who were MD/PhDs varied between 2.9 and 5.9 per 100 residents, with no significant change over time. There was also no change in the percentage of MD/PhDs entering psychiatry from among all MD/PhD graduates. The rate of increase in the number of MD/PhDs going into psychiatry did not differ significantly from other specialties except for family medicine, which is decreasing. The rate of MD/PhDs going into psychiatry was higher for women, suggesting closure of the sex gap in 17 years. Despite the increase in the number of MD/PhDs entering psychiatry, these numbers remain low. Expanding the cohort of physician-scientists dedicated to translational research in psychiatry will require a multipronged approach.

Analysis of the MdMYB1 gene sequence and development of new molecular markers related to apple skin color and fruit-bearing traits.

PubMed

Yuan, Kejun; Wang, Changjun; Wang, Jianghui; Xin, Li; Zhou, Guangfang; Li, Linguang; Shen, Guangning

2014-12-01

MdMYB1, a key transcription factor determining apple skin color, coordinately regulates genes in the anthocyanin pathway. In this study, we analyzed the MdMYB1 gene and its relationship to apple skin color and fruit-bearing traits to better understand this gene and its application to apple breeding. A previously reported MdMYB1 dCAPS marker failed to identify alleles of the MdMYB1 gene in 'Fuji', a very important apple cultivar. In this study, we revealed that the polymorphic site related to the MdMYB1 dCAPS marker is heterozygous in 'Fuji'. In addition, two new polymorphic sites related to apple skin color were identified in the MdMYB1 gene, with two new molecular markers accordingly developed. Testing of these markers in 'Fuji' and its progeny revealed that they could predict apple skin color and identify alleles of the MdMYB1 gene in this cultivar. Most interestingly, the allele MdMYB1-2 in 'Gala' apple and its hybrid plants was found to be related to the fruit-bearing trait, and the molecular marker Mb2 was able to identify the MdMYB1-2 allele. Our study is apparently the first to report a relationship between the MdMYB1 allele and the fruit-bearing trait in apple. More work is needed to determine whether and how the MdMYB1 gene or a gene linked to the MdMYB1-2 allele influences the flowering trait in perennial apple trees, and whether flowering in other plants is influenced by related genes.

Gaussian Accelerated Molecular Dynamics in NAMD.

PubMed

Pang, Yui Tik; Miao, Yinglong; Wang, Yi; McCammon, J Andrew

2017-01-10

Gaussian accelerated molecular dynamics (GaMD) is a recently developed enhanced sampling technique that provides efficient free energy calculations of biomolecules. Like the previous accelerated molecular dynamics (aMD), GaMD allows for "unconstrained" enhanced sampling without the need to set predefined collective variables and so is useful for studying complex biomolecular conformational changes such as protein folding and ligand binding. Furthermore, because the boost potential is constructed using a harmonic function that follows Gaussian distribution in GaMD, cumulant expansion to the second order can be applied to recover the original free energy profiles of proteins and other large biomolecules, which solves a long-standing energetic reweighting problem of the previous aMD method. Taken together, GaMD offers major advantages for both unconstrained enhanced sampling and free energy calculations of large biomolecules. Here, we have implemented GaMD in the NAMD package on top of the existing aMD feature and validated it on three model systems: alanine dipeptide, the chignolin fast-folding protein, and the M 3 muscarinic G protein-coupled receptor (GPCR). For alanine dipeptide, while conventional molecular dynamics (cMD) simulations performed for 30 ns are poorly converged, GaMD simulations of the same length yield free energy profiles that agree quantitatively with those of 1000 ns cMD simulation. Further GaMD simulations have captured folding of the chignolin and binding of the acetylcholine (ACh) endogenous agonist to the M 3 muscarinic receptor. The reweighted free energy profiles are used to characterize the protein folding and ligand binding pathways quantitatively. GaMD implemented in the scalable NAMD is widely applicable to enhanced sampling and free energy calculations of large biomolecules.

Quantitative Assessment of Molecular Dynamics Sampling for Flexible Systems.

PubMed

Nemec, Mike; Hoffmann, Daniel

2017-02-14

Molecular dynamics (MD) simulation is a natural method for the study of flexible molecules but at the same time is limited by the large size of the conformational space of these molecules. We ask by how much the MD sampling quality for flexible molecules can be improved by two means: the use of diverse sets of trajectories starting from different initial conformations to detect deviations between samples and sampling with enhanced methods such as accelerated MD (aMD) or scaled MD (sMD) that distort the energy landscape in controlled ways. To this end, we test the effects of these approaches on MD simulations of two flexible biomolecules in aqueous solution, Met-Enkephalin (5 amino acids) and HIV-1 gp120 V3 (a cycle of 35 amino acids). We assess the convergence of the sampling quantitatively with known, extensive measures of cluster number N c and cluster distribution entropy S c and with two new quantities, conformational overlap O conf and density overlap O dens , both conveniently ranging from 0 to 1. These new overlap measures quantify self-consistency of sampling in multitrajectory MD experiments, a necessary condition for converged sampling. A comprehensive assessment of sampling quality of MD experiments identifies the combination of diverse trajectory sets and aMD as the most efficient approach among those tested. However, analysis of O dens between conventional and aMD trajectories also reveals that we have not completely corrected aMD sampling for the distorted energy landscape. Moreover, for V3, the courses of N c and O dens indicate that much higher resources than those generally invested today will probably be needed to achieve convergence. The comparative analysis also shows that conventional MD simulations with insufficient sampling can be easily misinterpreted as being converged.

Expression of MdCAS1 and MdCAS2, encoding apple beta-cyanoalanine synthase homologs, is concomitantly induced during ripening and implicates MdCASs in the possible role of the cyanide detoxification in Fuji apple (Malus domestica Borkh.) fruits.

PubMed

Han, Sang Eun; Seo, Young Sam; Kim, Daeil; Sung, Soon-Kee; Kim, Woo Taek

2007-08-01

Fruit ripening involves complex biochemical and physiological changes. Ethylene is an essential hormone for the ripening of climacteric fruits. In the process of ethylene biosynthesis, cyanide (HCN), an extremely toxic compound, is produced as a co-product. Thus, most cyanide produced during fruit ripening should be detoxified rapidly by fruit cells. In higher plants, the key enzyme involved in the detoxification of HCN is beta-cyanoalanine synthase (beta-CAS). As little is known about the molecular function of beta-CAS genes in climacteric fruits, we identified two homologous genes, MdCAS1 and MdCAS2, encoding Fuji apple beta-CAS homologs. The structural features of the predicted polypeptides as well as an in vitro enzyme activity assay with bacterially expressed recombinant proteins indicated that MdCAS1 and MdCAS2 may indeed function as beta-CAS isozymes in apple fruits. RNA gel-blot studies revealed that both MdCAS1 and MdCAS2 mRNAs were coordinately induced during the ripening process of apple fruits in an expression pattern comparable with that of ACC oxidase and ethylene production. The MdCAS genes were also activated effectively by exogenous ethylene treatment and mechanical wounding. Thus, it seems like that, in ripening apple fruits, expression of MdCAS1 and MdCAS2 genes is intimately correlated with a climacteric ethylene production and ACC oxidase activity. In addition, beta-CAS enzyme activity was also enhanced as the fruit ripened, although this increase was not as dramatic as the mRNA induction pattern. Overall, these results suggest that MdCAS may play a role in cyanide detoxification in ripening apple fruits.

Gerstmann-Straussler-Scheinker Disease

MedlinePlus

... NIA) National Institutes of Health, DHHS 31 Center Drive, Rm. 5C27 MSC 2292 Bethesda MD Bethesda, MD ... NIA) National Institutes of Health, DHHS 31 Center Drive, Rm. 5C27 MSC 2292 Bethesda MD Bethesda, MD ...

[The effects of hatha yoga exercises on stress and anxiety levels in mastectomized women].

PubMed

Bernardi, Marina Lima Daleprane; Amorim, Maria Helena Costa; Zandonade, Eliana; Santaella, Danilo Forghieri; Barbosa, Juliana de Assis Novais

2013-12-01

This article seeks to evaluate the effects of hatha yoga on stress and anxiety levels in mastectomized women. It also investigates the relationship between these levels with the following variables: age; marital status; religion; instruction; profession; smoke addiction; elitism; staging of the disease; and treatment phase. This involved controlled random clinical trial sampling of 45 mastectomized women treated at the Ilza Bianco outpatient service of Santa Rita de Cássia Hospital in the Brazilian state of Espírito Santo from March to November 2010. The experimental group participated in 6 individually-applied sessions with incentive for ongoing home practice and was re-evaluated after the period, whereas the control group was re-evaluated after a proportional period. For the study of the variables, the interview and recording on a form technique was used, along with the Anxiety Trait and State Test, and the Stress Symptoms and Signs Test. For statistical treatment, the Statistical Pack for Social Sciences was used. The data are statistically significant and have shown that hatha yoga exercises decrease stress and anxiety in the experimental group. No connection between confounding variables and anxiety and stress levels was found.

Enhanced recovery after surgery and video-assisted thoracic surgery lobectomy: the Italian VATS Group**List of collaborators of the Italian ERAS Group: Jacopo Vannucci, MD (University of Perugia); Antonio D’Andrilli, MD (S. Andrea Hospital, Roma); Majed Refai, MD (Ospedali Riuniti, Ancona); Guendalina Graffigna, MD (Università Cattolica del Sacro Cuore, Milano); Stefano Lovadina, MD (Ospedali Riuniti, Trieste); Marzia Umari (Ospedali Riuniti, Trieste), Paolo Ferrari, MD (IRCCS ISMETT-UPMC, University of Pittsburgh, Palermo); Michele Zuliani, MD (Ospedali Riuniti, Trieste); Marco Taurchini, MD (Casa Sollievo della Sofferenza, San Giovanni Rotondo); Carlo Del Naja, MD (Casa Sollievo della Sofferenza, San Giovanni Rotondo); Domenico Massullo, MD (S. Andrea Hospital, Roma), Olha Putina, MD (ASST Mantova), Nicoletta Pia Ardò (University of Foggia). surgical protocol

PubMed Central

Viggiano, Domenico; Voltolini, Luca; Bertani, Alessandro; Bertolaccini, Luca; Crisci, Roberto; Droghetti, Andrea

2018-01-01

Enhanced recovery after surgery (ERAS®) is a strategy that seeks to reduce patients’ perioperative stress response, thereby reducing potential complications, decreasing hospital length of stay and enabling patients to return more quickly to their baseline functional status. The concept was introduced in the late 1990s and was first adopted in patients undergoing open colorectal surgery. Since then, the concept of ERAS has been adopted by multiple surgical specialties. The diffusion of video-assisted thoracic surgery lobectomy (VATS-L) sets also the surgical treatment of lung cancer as a new area for ERAS development. In this paper, we present the Italian VATS Group (www.vatsgroup.org) surgical protocol as part of the ERAS clinical pathway belonging to the VATS-L national database. PMID:29629203

Celastrol reverses palmitic acid (PA)-caused TLR4-MD2 activation-dependent insulin resistance via disrupting MD2-related cellular binding to PA.

PubMed

Zhang, Xue; Wang, Ying; Ge, Hui-Ya; Gu, Yi-Jun; Cao, Fan-Fan; Yang, Chun-Xin; Uzan, Georges; Peng, Bin; Zhang, Deng-Hai

2018-04-18

Elevated plasma statured fatty acids (FFAs) cause TLR4/MD2 activation-dependent inflammation and insulin tolerance, which account for the occurrence and development of obesity. It has been confirmed that statured palmitic acid (PA) (the most abundant FFA) could bind MD2 to cause cellular inflammation. The natural compound celastrol could improve obesity, which is suggested via inhibiting inflammation, yet the detailed mechanism for celastrol is still unclear. As celastrol is reported to directly target MD2, we thought disrupting the binding between FFAs and MD2 might be one of the ways for celastrol to inhibit FFAs-caused inflammation and insulin resistance. In this study, we found evidence to support our hypothesis: celastrol could reverse PA-caused TLR4/MD2 activation-dependent insulin resistance, as determined by glucose-lowering ability, cellular glucose uptake, insulin action-related proteins and TLR4/MD2/NF-κB activation. Bioinformatics and cellular experiments showed that both celastrol and PA could bind MD2, and that celastrol could expel PA from cells. Finally, celastrol could reverse high fat diet caused hyperglycemia and obesity, and liver NF-kB activations. Taking together, we proved that celastrol could reverses PA-caused TLR4-MD2 activation-dependent insulin resistance via disrupting PA binding to MD2. © 2018 Wiley Periodicals, Inc.

Clinical Investigation Program Annual Progress Report

DTIC Science & Technology

1989-10-01

Investigators: Linda K. Kullama, Ph.D., Dr. Kenneth T. Nakamura,MD; Dr. Venkataraman Balaraman, MD, Wayne M. Ichimura, Biomedical Engineer. Department/Section...Investigators: John R. Claybaugh, Ph.D.; Kenneth T. Nakamura, MD; Dr. Venkataraman Balaraman, M.D. Department/Section: Clinical Investigation/Physiology Key...Pigs and Rats Principal ’Investigator: Linda K. Kullama, Ph.D.; John R. Claybaugh, Ph.D. Associate Investigators: Dr. Venkataraman Balaraman, M.D.; Dr

Clinical Investigation Program, Reports Control Symbol MED-300(R1), Fiscal Year 1988

DTIC Science & Technology

1988-10-01

Dr. Venkataraman Balaraman, M.D. Department/Section: Clinical Investigation Key Words: arginine vasopressin (AVP); vascular smooth muscle responses...Kullama, Ph.D. Associate Investigators: Dr. Venkataraman Balaraman, M.D.; Dr. Kenneth T. Nakamura, M.D.; John R. Claybaugh, Ph.D. Department/Section...Harrison Hassell, MC Associate Investigators: John R. Claybaugh, Ph.D.; Arnold Siemsen, MD; Jon Streltzer, MD Department/Section: Medicine/ Nephrology

33 CFR 334.180 - Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md.

Code of Federal Regulations, 2013 CFR

2013-07-01

.... Naval Mine Warfare Test Station, or of U.S. Naval Air Station property. A person in the water or a... areas, U.S. Naval Air Test Center, Patuxent River, Md. 334.180 Section 334.180 Navigation and Navigable... REGULATIONS § 334.180 Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md...

33 CFR 334.180 - Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... Naval Mine Warfare Test Station, or of U.S. Naval Air Station property. A person in the water or a... areas, U.S. Naval Air Test Center, Patuxent River, Md. 334.180 Section 334.180 Navigation and Navigable... REGULATIONS § 334.180 Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md...

33 CFR 334.180 - Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md.

Code of Federal Regulations, 2012 CFR

2012-07-01

.... Naval Mine Warfare Test Station, or of U.S. Naval Air Station property. A person in the water or a... areas, U.S. Naval Air Test Center, Patuxent River, Md. 334.180 Section 334.180 Navigation and Navigable... REGULATIONS § 334.180 Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md...

33 CFR 334.180 - Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... Naval Mine Warfare Test Station, or of U.S. Naval Air Station property. A person in the water or a... areas, U.S. Naval Air Test Center, Patuxent River, Md. 334.180 Section 334.180 Navigation and Navigable... REGULATIONS § 334.180 Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md...

33 CFR 334.180 - Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... Naval Mine Warfare Test Station, or of U.S. Naval Air Station property. A person in the water or a... areas, U.S. Naval Air Test Center, Patuxent River, Md. 334.180 Section 334.180 Navigation and Navigable... REGULATIONS § 334.180 Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md...

Trapped in a Daydream: Daily Elevations in Maladaptive Daydreaming Are Associated With Daily Psychopathological Symptoms.

PubMed

Soffer-Dudek, Nirit; Somer, Eli

2018-01-01

Background: Maladaptive Daydreaming (MD) characterizes individuals who engage in vivid, fanciful daydreaming for hours on end, neglecting real-life relationships and responsibilities, resulting in clinical distress and functional impairment. Sufferers have embraced the term MD in cyber-communities devoted to this problem because it seemed to uniquely fit their experience and since existing diagnostic labels and their therapies seemed inadequate. However, scientific research in the field has been scarce, relying on cross-sectional or case study designs. Existing knowledge on MD suggests the involvement of dissociative and obsessive-compulsive symptoms, as well as positive reinforcement comparable to processes in addiction disorders. The present study aimed to rigorously explore factors that accompany MD employing a longitudinal daily-diary design, hypothesizing that temporal increases in MD will associate concurrently with, and will temporally precede, other symptoms and emotional changes. In addition, we aimed to explore which symptoms may act as precursors to increases in MD, in order to identify possible mechanisms bringing about daydreaming in these individuals. Methods: In a sample of 77 self-diagnosed individuals with MD we assessed relevant daily symptoms for 14 days, including MD, depression, general anxiety, social anxiety, obsessive-compulsive symptoms, and dissociation, as well as positive and negative emotion. Results: Increases in MD were strongly related to concurrent increases in all other symptoms and negative emotion, and to decreased positive emotion. Obsessive-compulsive symptoms, dissociation, and negative emotion also temporally followed MD. Obsessive-compulsive symptoms were the only consistent temporal antecedent of MD. Conclusions: MD and obsessive-compulsive symptoms coincided in what seems to be a vicious cycle; understanding possible shared mechanisms between these symptoms may inform our understanding of the etiology of MD. For example, Serotonin levels may possibly be involved in the development or maintenance of this condition. The findings may also provide clues as to potentially beneficial interventions for treating MD. For example, perhaps utilizing response prevention techniques may be useful for curbing or intercepting unwanted daydreaming. Future studies on MD should address its compulsory nature.

Apple fruit copper amine oxidase isoforms: peroxisomal MdAO1 prefers diamines as substrates, whereas extracellular MdAO2 exclusively utilizes monoamines.

PubMed

Zarei, Adel; Trobacher, Christopher P; Cooke, Alison R; Meyers, Ashley J; Hall, J Christopher; Shelp, Barry J

2015-01-01

4-Aminobutyrate (GABA) accumulates in apple fruit during controlled atmosphere storage. A potential source of GABA is the polyamine putrescine, which can be oxidized via copper-containing amine oxidase (CuAO), resulting in the production 4-aminobutanal/Δ(1)-pyrroline, with the consumption of O2 and release of H2O2 and ammonia. Five putative CuAO genes (MdAO genes) were cloned from apple (Malus domestica Borkh. cv. Empire) fruit, and the deduced amino acid sequences found to contain the active sites typically conserved in CuAOs. Genes encoding two of these enzymes, MdAO1 and MdAO2, were highly expressed in apple fruit and selected for further analysis. Amino acid sequence analysis predicted the presence of a C-terminal peroxisomal targeting signal 1 tripeptide in MdAO1 and an N-terminal signal peptide and N-glycosylation site in MdAO2. Transient expression of green fluorescent fusion proteins in Arabidopsis protoplasts or onion epidermal cells revealed a peroxisomal localization for MdAO1 and an extracellular localization for MdAO2. The enzymatic activities of purified recombinant MdAO1 and MdAO2 were measured continuously as H2O2 production using a coupled reaction. MdAO1 did not use monoamines or polyamines and displayed high catalytic efficiency for 1,3-diaminopropane, putrescine and cadaverine, whereas MdAO2 exclusively utilized aliphatic and aromatic monoamines, including 2-phenylethylamine and tyramine. Together, these results indicate that MdAO1 may contribute to GABA production via putrescine oxidation in the peroxisome of apple fruit under controlled atmosphere conditions. MdAO2 seems to be involved in deamination of 2-phenylethylamine, which is a step in the biosynthesis of 2-phenylethanol, a contributor to fruit flavor and flower fragrance. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Assessing the allelotypic effect of two aminocyclopropane carboxylic acid synthase-encoding genes MdACS1 and MdACS3a on fruit ethylene production and softening in Malus

PubMed Central

Dougherty, Laura; Zhu, Yuandi; Xu, Kenong

2016-01-01

Phytohormone ethylene largely determines apple fruit shelf life and storability. Previous studies demonstrated that MdACS1 and MdACS3a, which encode 1-aminocyclopropane-1-carboxylic acid synthases (ACS), are crucial in apple fruit ethylene production. MdACS1 is well-known to be intimately involved in the climacteric ethylene burst in fruit ripening, while MdACS3a has been regarded a main regulator for ethylene production transition from system 1 (during fruit development) to system 2 (during fruit ripening). However, MdACS3a was also shown to have limited roles in initiating the ripening process lately. To better assess their roles, fruit ethylene production and softening were evaluated at five time points during a 20-day post-harvest period in 97 Malus accessions and in 34 progeny from 2 controlled crosses. Allelotyping was accomplished using an existing marker (ACS1) for MdACS1 and two markers (CAPS866 and CAPS870) developed here to specifically detect the two null alleles (ACS3a-G289V and Mdacs3a) of MdACS3a. In total, 952 Malus accessions were allelotyped with the three markers. The major findings included: The effect of MdACS1 was significant on fruit ethylene production and softening while that of MdACS3a was less detectable; allele MdACS1–2 was significantly associated with low ethylene and slow softening; under the same background of the MdACS1 allelotypes, null allele Mdacs3a (not ACS3a-G289V) could confer a significant delay of ethylene peak; alleles MdACS1–2 and Mdacs3a (excluding ACS3a-G289V) were highly enriched in M. domestica and M. hybrid when compared with those in M. sieversii. These findings are of practical implications in developing apples of low and delayed ethylene profiles by utilizing the beneficial alleles MdACS1-2 and Mdacs3a. PMID:27231553

Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis

PubMed Central

Rossignol, D A; Frye, R E

2012-01-01

A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (∼0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD. PMID:21263444

Symptoms of muscle dysmorphia, body dysmorphic disorder, and eating disorders in a nonclinical population of adult male weightlifters in Australia.

PubMed

Nieuwoudt, Johanna E; Zhou, Shi; Coutts, Rosanne A; Booker, Ray

2015-05-01

The current study aimed to (a) determine the rates of symptoms of muscle dysmorphia (MD), body dysmorphic disorder (BDD), and eating disorder; (b) determine the relationships among symptoms of MD, BDD, and eating disorders; and (c) provide a comprehensive comparison of symptoms of MD, BDD, and eating disorders in a nonclinical population of adult male weightlifters in Australia. The participants (N = 648, mean age = 29.5 years, SD = 10.1) participated in an online survey, consisting of Muscle Appearance Satisfaction Scale, the Body Dysmorphic Disorder Questionnaire, and the Eating Attitude Test-26. Results indicated that 110 participants (17%) were at risk of having MD, 69 participants (10.6%) were at risk of having BDD, and 219 participants (33.8%) were at risk of having an eating disorder. Furthermore, 36 participants (5.6%) were found at risk of having both MD and BDD, and 60 participants (9.3%) were at risk of having both MD and an eating disorder. Significant correlations and associations were found between symptoms of MD and BDD, and symptoms of MD and eating disorders. Support was provided for the comorbidity of, and symptomatic similarities between, symptoms of MD and BDD, and symptoms of MD and eating disorders. This may reflect a shared pathogenesis between symptoms of MD, BDD, and eating disorders. Strength and conditioning professionals, exercise scientists, athletic trainers, and personal trainers should be aware that adult males who are working out with weights (i.e., free weights or machines) may be at increased risk of having MD, BDD, and eating disorders.

A novel triazine ring compound (MD568) exerts in vivo and in vitro effects on lipid metabolism.

PubMed

Jia, Dan; Li, Ziwen; Gao, Ying; Feng, Yifan; Li, Weimin

2018-07-01

In this study, we investigated the toxicity and biological activity of a novel triazine ring compound named magnolol derivative 568 (MD568). The LD 50 of MD568 was determined in Sprague-Dawley (SD) rats by intraperitoneal injection. Treatment of high fat diet-induced obese rats with MD568 demonstrated that MD568 displayed significant anti-obesity effects. MD568 markedly reduced body weight, blood lipid contents, white adipose tissue (WAT) and liver mass in obese rats. In addition, MD568 modulated lesions in WAT through regulating PPAR-Ɣ, C/EBP-a, SREBP-1c and FABP-4 proteins in the liver through regulating PPAR-α, SREBP-1c and FABP-4. We also evaluated the effects of MD568 on the proliferation and differentiation of 3T3-L1 pre-adipocytes and investigated the underlying mechanism by microarray analysis. Results showed that MD568 has good inhibitory activity on lipogenesis and lipid accumulation in 3T3-L1 pre-adipocytes. The protein expression levels of the adipogenic transcription factors PPAR-Ɣ, C/EBP-a, SREBP-1c and FABP-4 were reduced by MD568. In addition, the gene expression of FAS and LDL was also significantly down-regulated by MD568. Microarray data enrichment analysis demonstrated that the underlying mechanism of action of MD568 may be related to its regulatory effects on genes associated with the biological processes or pathways in lipid metabolism. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Registration of five upland cotton mutant germplasm lines with superior fiber length, strength, and uniformity

USDA-ARS?s Scientific Manuscript database

Mutant germplasm lines MD 15-Mut 13 (Reg. No. GP-1025, PI 681706), MD 15-Mut 31 (Reg. No. GP-1026, PI 681707), MD 15-Mut 61 (Reg. No. GP-1027, PI 681708), MD 15-Mut 89 (Reg. No. GP-1028, PI 681709), and MD 15-Mut 138 (Reg. No. GP-1029, PI 681710) are unique genotypes of upland cotton (Gossypium hirs...

VIEW IN OPPOSITE DIRECTION AS MD1351 AND MD1352. RAW MATERIAL ...

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

VIEW IN OPPOSITE DIRECTION AS MD-135-1 AND MD-135-2. RAW MATERIAL CONVEYOR AT LEFT DEPOSITS SHELL INTO MILLING MACHINE AT LOWER LEFT. ENGINE IS AT LOWER RIGHT AND RADIATOR AT LOWER CENTER. ROLLER SORTER IS AT TOP OF CONVEYOR. - F. & H. Benning Company Oyster Mill, 14430 Solomons Island Road (moved from 1014 Benning Road, Galesville, Anne Arundel County, Maryland), Solomons, Calvert County, MD

The bZIP transcription factor MdHY5 regulates anthocyanin accumulation and nitrate assimilation in apple.

PubMed

An, Jian-Ping; Qu, Feng-Jia; Yao, Ji-Fang; Wang, Xiao-Na; You, Chun-Xiang; Wang, Xiao-Fei; Hao, Yu-Jin

2017-01-01

The basic leucine zipper (bZIP) transcription factor HY5 plays a multifaceted role in plant growth and development. Here the apple MdHY5 gene was cloned based on its homology with Arabidopsis HY5 . Expression analysis demonstrated that MdHY5 transcription was induced by light and abscisic acid treatments. Electrophoretic mobility shift assays and transient expression assays subsequently showed that MdHY5 positively regulated both its own transcription and that of MdMYB10 by binding to E-box and G-box motifs, respectively. Furthermore, we obtained transgenic apple calli that overexpressed the MdHY5 gene, and apple calli coloration assays showed that MdHY5 promoted anthocyanin accumulation by regulating expression of the MdMYB10 gene and downstream anthocyanin biosynthesis genes. In addition, the transcript levels of a series of nitrate reductase genes and nitrate uptake genes in both wild-type and transgenic apple calli were detected. In association with increased nitrate reductase activities and nitrate contents, the results indicated that MdHY5 might be an important regulator in nutrient assimilation. Taken together, these results indicate that MdHY5 plays a vital role in anthocyanin accumulation and nitrate assimilation in apple.

CAPTURE OF FREE-RANGING MULE DEER (ODOCOILEUS HEMIONUS) WITH A COMBINATION OF MEDETOMIDINE, AZAPERONE, AND ALFAXALONE.

PubMed

Mathieu, Amélie; Caulkett, Nigel; Stent, Patrick M; Schwantje, Helen M

2017-04-01

The combination of medetomidine, azaperone, and alfaxalone has been successfully used to anesthetize captive white-tailed deer ( Odocoileus virginianus ). This same combination was utilized to immobilize free-ranging female mule deer ( Odocoileus hemionus ; MD) in urban and nonurban environments (14 urban MD, 14 nonurban MD) in British Columbia, Canada. Physiologic data were collected to assess the safety and reliability of this drug combination under field conditions. Each deer received estimated dosages of 0.15 mg/kg medetomidine, 0.2 mg/kg azaperone, and 0.5 mg/kg alfaxalone intramuscularly via a remote darting system. Inductions were calm and rapid (mean time to sternal recumbency: urban MD, 6.4±2.2 min; nonurban MD, 8.2±4.1 min). Supplemental drugs were required to induce lateral recumbency in five deer, four of which had experienced initial dart failure (mean time to lateral recumbency: urban MD, 8.5±3.8 min; nonurban MD, 18.7±16.5 min). Recoveries were smooth and uneventful (time to standing: urban MD, 12.5±3.4 min; nonurban MD, 9.0±3.5 min) for all but one debilitated nonurban MD that died shortly after atipamezole administration (at five times the medetomidine dose). The major side effects of the combination were hypoxemia and hypercapnia. The combination of medetomidine, azaperone, and alfaxalone proved suitable for the immobilization of urban and nonurban free-ranging MD.

Angiotensin II induces kidney inflammatory injury and fibrosis through binding to myeloid differentiation protein-2 (MD2).

PubMed

Xu, Zheng; Li, Weixin; Han, Jibo; Zou, Chunpeng; Huang, Weijian; Yu, Weihui; Shan, Xiaoou; Lum, Hazel; Li, Xiaokun; Liang, Guang

2017-03-21

Growing evidence indicates that angiotensin II (Ang II), a potent biologically active product of RAS, is a key regulator of renal inflammation and fibrosis. In this study, we tested the hypothesis that Ang II induces renal inflammatory injury and fibrosis through interaction with myeloid differentiation protein-2 (MD2), the accessory protein of toll-like receptor 4 (TLR4) of the immune system. Results indicated that in MD2 -/- mice, the Ang II-induced renal fibrosis, inflammation and kidney dysfunction were significantly reduced compared to control Ang II-infused wild-type mice. Similarly, in the presence of small molecule MD2 specific inhibitor L6H21 or siRNA-MD2, the Ang II-induced increases of pro-fibrotic and pro-inflammatory molecules were prevented in tubular NRK-52E cells. MD2 blockade also inhibited activation of NF-κB and ERK. Moreover, MD2 blockade prevented the Ang II-stimulated formation of the MD2/TLR4/MyD88 signaling complex, as well as the increased surface binding of Ang II in NRK-52E cells. In addition, Ang II directly bound recombinant MD2 protein, rather than TLR4 protein. We conclude that MD2 is a significant contributor in the Ang II-induced kidney inflammatory injury in chronic renal diseases. Furthermore, MD2 inhibition could be a new and important therapeutic strategy for preventing progression of chronic renal diseases.

MdMYB1 Regulates Anthocyanin and Malate Accumulation by Directly Facilitating Their Transport into Vacuoles in Apples1[OPEN

PubMed Central

Hu, Da-Gang; Sun, Cui-Hui; Ma, Qi-Jun; You, Chun-Xiang; Hao, Yu-Jin

2016-01-01

Tonoplast transporters, including proton pumps and secondary transporters, are essential for plant cell function and for quality formation of fleshy fruits and ornamentals. Vacuolar transport of anthocyanins, malate, and other metabolites is directly or indirectly dependent on the H+-pumping activities of vacuolar H+-ATPase (VHA) and/or vacuolar H+-pyrophosphatase, but how these proton pumps are regulated in modulating vacuolar transport is largely unknown. Here, we report a transcription factor, MdMYB1, in apples that binds to the promoters of two genes encoding the B subunits of VHA, MdVHA-B1 and MdVHA-B2, to transcriptionally activate its expression, thereby enhancing VHA activity. A series of transgenic analyses in apples demonstrates that MdMYB1/10 controls cell pH and anthocyanin accumulation partially by regulating MdVHA-B1 and MdVHA-B2. Furthermore, several other direct target genes of MdMYB10 are identified, including MdVHA-E2, MdVHP1, MdMATE-LIKE1, and MdtDT, which are involved in H+-pumping or in the transport of anthocyanins and malates into vacuoles. Finally, we show that the mechanism by which MYB controls malate and anthocyanin accumulation in apples also operates in Arabidopsis (Arabidopsis thaliana). These findings provide novel insights into how MYB transcription factors directly modulate the vacuolar transport system in addition to anthocyanin biosynthesis, consequently controlling organ coloration and cell pH in plants. PMID:26637549

MdMYB1 Regulates Anthocyanin and Malate Accumulation by Directly Facilitating Their Transport into Vacuoles in Apples.

PubMed

Hu, Da-Gang; Sun, Cui-Hui; Ma, Qi-Jun; You, Chun-Xiang; Cheng, Lailiang; Hao, Yu-Jin

2016-03-01

Tonoplast transporters, including proton pumps and secondary transporters, are essential for plant cell function and for quality formation of fleshy fruits and ornamentals. Vacuolar transport of anthocyanins, malate, and other metabolites is directly or indirectly dependent on the H(+)-pumping activities of vacuolar H(+)-ATPase (VHA) and/or vacuolar H(+)-pyrophosphatase, but how these proton pumps are regulated in modulating vacuolar transport is largely unknown. Here, we report a transcription factor, MdMYB1, in apples that binds to the promoters of two genes encoding the B subunits of VHA, MdVHA-B1 and MdVHA-B2, to transcriptionally activate its expression, thereby enhancing VHA activity. A series of transgenic analyses in apples demonstrates that MdMYB1/10 controls cell pH and anthocyanin accumulation partially by regulating MdVHA-B1 and MdVHA-B2. Furthermore, several other direct target genes of MdMYB10 are identified, including MdVHA-E2, MdVHP1, MdMATE-LIKE1, and MdtDT, which are involved in H(+)-pumping or in the transport of anthocyanins and malates into vacuoles. Finally, we show that the mechanism by which MYB controls malate and anthocyanin accumulation in apples also operates in Arabidopsis (Arabidopsis thaliana). These findings provide novel insights into how MYB transcription factors directly modulate the vacuolar transport system in addition to anthocyanin biosynthesis, consequently controlling organ coloration and cell pH in plants. © 2016 American Society of Plant Biologists. All Rights Reserved.

Genetic and environmental influences on last-year major depression in adulthood: a highly heritable stable liability but strong environmental effects on 1-year prevalence.

PubMed

Kendler, K S; Gardner, C O

2017-07-01

This study seeks to clarify the contribution of temporally stable and occasion-specific genetic and environmental influences on risk for major depression (MD). Our sample was 2153 members of female-female twin pairs from the Virginia Twin Registry. We examined four personal interview waves conducted over an 8-year period with MD in the last year defined by DSM-IV criteria. We fitted a structural equation model to the data using classic Mx. The model included genetic and environmental risk factors for a latent, stable vulnerability to MD and for episodes in each of the four waves. The best-fit model was simple and included genetic and unique environmental influences on the latent liability to MD and unique wave-specific environmental effects. The path from latent liability to MD in the last year was constant over time, moderate in magnitude (+0.65) and weaker than the impact of occasion-specific environmental effects (+0.76). Heritability of the latent stable liability to MD was much higher (78%) than that estimated for last-year MD (32%). Of the total unique environmental influences on MD, 13% reflected enduring consequences of earlier environmental insults, 17% diagnostic error and 70% wave-specific short-lived environmental stressors. Both genetic influences on MD and MD heritability are stable over middle adulthood. However, the largest influence on last-year MD is short-lived environmental effects. As predicted by genetic theory, the heritability of MD is increased substantially by measurement at multiple time points largely through the reduction of the effects of measurement error and short-term environmental risk factors.

Myeloid differentiation protein 2-dependent mechanisms in retinal ischemia-reperfusion injury

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

Ren, Luqing

Retinal ischemia-reperfusion (I/R) injury is a common pathological process in many eye disorders. Oxidative stress and inflammation play a role in retinal I/R injury. Recent studies show that toll-like receptor 4 (TLR4) is involved in initiating sterile inflammatory response in retinal I/R. However, the molecular mechanism by which TLR4 is activated is not known. In this study, we show that retinal I/R injury involves a co-receptor of TLR4, myeloid differentiation 2 (MD2). Inhibition of MD2 prevented cell death and preserved retinal function following retinal I/R injury. We confirmed these findings using MD2 knockout mice. Furthermore, we utilized human retinal pigmentmore » epithelial cells (ARPE-19 cells) to show that oxidative stress-induced cell death as well as inflammatory response are mediated through MD2. Inhibition of MD2 through a chemical inhibitor or knockdown prevented oxidative stress-induced cell death and expression of inflammatory cytokines. Oxidative stress was found to activate TLR4 in a MD2-dependent manner via increasing the expression of high mobility group box 1. In summary, our study shows that oxidative stress in retinal I/R injury can activate TLR4 signaling via MD2, resulting in induction of inflammatory genes and retinal damage. MD2 may represent an attractive therapeutic target for retinal I/R injury. - Highlights: • MD2 inhibition reduced retinal damage after I/R induction in mice. • TBHP induced TLR4/MD2 binding via increasing HMGB-1 expression. • TLR4/MD2 initiated inflammatory response via activation of MAPKs and NF-κB. • MD2 could be the therapeutic target for the treatment of retinal I/R.« less

Identification and expression analysis of the IPT and CKX gene families during axillary bud outgrowth in apple (Malus domestica Borkh.).

PubMed

Tan, Ming; Li, Guofang; Qi, Siyan; Liu, Xiaojie; Chen, Xilong; Ma, Juanjuan; Zhang, Dong; Han, Mingyu

2018-04-20

Cytokinins (CKs) play a crucial role in promoting axillary bud outgrowth and targeting the control of CK metabolism can be used to enhance branching in plants. CK levels are maintained mainly by CK biosynthesis (isopentenyl transferase, IPT) and degradation (dehydrogenase, CKX) genes in plants. A systematic study of the IPT and CKX gene families in apple, however, has not been conducted. In the present study, 12 MdIPTs and 12 MdCKXs were identified in the apple genome. Systematic phylogenetic, structural, and synteny analyses were performed. Expression analysis of these genes in different tissues was also assessed. MdIPT and MdCKX genes exhibit distinct expression patterns in different tissues. The response of MdIPT, MdCKX, and MdPIN1 genes to various treatments (6-BA, decapitation and Lovastatin, an inhibitor of CKs synthesis) that impact branching were also investigated. Results indicated that most of the MdIPT and MdCKX, and MdPIN1 genes were upregulated by 6-BA and decapitation treatment, but inhibited by Lovastatin, a compound that effectively suppresses axillary bud outgrowth induced by decapitation. These findings suggest that cytokinin biosynthesis is required for the activation of bud break and the export of auxin from buds in apple tree with intact primary shoot apex or decapitated apple tree. MdCKX8 and MdCKX10, however, exhibited little response to decapitation, but were significantly up-regulated by 6-BA and Lovastatin, a finding that warrants further investigation in order to understand their function in bud-outgrowth. Copyright © 2018 Elsevier B.V. All rights reserved.

Relationship of Terminal Duct Lobular Unit Involution of the Breast with Area and Volume Mammographic Densities

PubMed Central

Gierach, Gretchen L.; Patel, Deesha A.; Pfeiffer, Ruth M.; Figueroa, Jonine D.; Linville, Laura; Papathomas, Daphne; Johnson, Jason M.; Chicoine, Rachael E.; Herschorn, Sally D.; Shepherd, John A.; Wang, Jeff; Malkov, Serghei; Vacek, Pamela M.; Weaver, Donald L.; Fan, Bo; Mahmoudzadeh, Amir Pasha; Palakal, Maya; Xiang, Jackie; Oh, Hannah; Horne, Hisani N.; Sprague, Brian L.; Hewitt, Stephen M.; Brinton, Louise A.; Sherman, Mark E.

2016-01-01

Elevated mammographic density (MD) is an established breast cancer risk factor. Reduced involution of terminal duct lobular units (TDLUs), the histologic source of most breast cancers, has been associated with higher MD and breast cancer risk. We investigated relationships of TDLU involution with area and volumetric MD, measured throughout the breast and surrounding biopsy targets (peri-lesional). Three measures inversely related to TDLU involution (TDLU count/mm2, median TDLU span, median acini count/TDLU) assessed in benign diagnostic biopsies from 348 women, ages 40–65, were related to MD area (quantified with thresholding software) and volume (assessed with a density phantom) by analysis of covariance, stratified by menopausal status and adjusted for confounders. Among premenopausal women, TDLU count was directly associated with percent peri-lesional MD (P-trend=0.03), but not with absolute dense area/volume. Greater TDLU span was associated with elevated percent dense area/volume (P-trend<0.05) and absolute peri-lesional MD (P=0.003). Acini count was directly associated with absolute peri-lesional MD (P=0.02). Greater TDLU involution (all metrics) was associated with increased nondense area/volume (P-trend≤0.04). Among postmenopausal women, TDLU measures were not significantly associated with MD. Among premenopausal women, reduced TDLU involution was associated with higher area and volumetric MD, particularly in peri-lesional parenchyma. Data indicating that TDLU involution and MD are correlated markers of breast cancer risk suggest that associations of MD with breast cancer may partly reflect amounts of at-risk epithelium. If confirmed, these results could suggest a prevention paradigm based on enhancing TDLU involution and monitoring efficacy by assessing MD reduction. PMID:26645278

Rates of glaucomatous visual field change in a large clinical population.

PubMed

Chauhan, Balwantray C; Malik, Rizwan; Shuba, Lesya M; Rafuse, Paul E; Nicolela, Marcelo T; Artes, Paul H

2014-06-10

To determine the rate of glaucomatous visual field change in routine clinical care. Mean deviation (MD) rate was computed in one randomly selected eye of all glaucoma patients and suspects with ≥5 examinations in a tertiary eye-care center. Proportions of "fast" (MD rate, <-1 to -2 dB/y) and "catastrophic" (<-2 dB/y) progressors were determined. The MD rates were computed in tertile groups by the number of examinations, baseline age, and MD. The MD rates were compared to the Canadian Glaucoma Study (CGS), a prospective study with IOP interventions mandated by visual field progression, by pairwise matching of patients by baseline MD. There were 2324 patients with median (interquartile range) baseline age and MD of 65 (56, 74) years and -2.44 (-5.44, -0.86) dB, and follow-up of 7.1 (4.8, 10.2) years with 8 (6, 11) examinations. The median MD rate was -0.05 (0.13, -0.30) dB/y, while the mean follow-up IOP was 17.1 (15.0, 19.7) mm Hg. The MD rate was progressively worse, with a doubling of fast and catastrophic progressors, with each tertile of increasing age. Worse MD rate was associated with lower follow-up IOP. Neither MD rate nor the number of fast and catastrophic progressors was significantly different in clinical care patients matched to CGS patients. Most patients under routine glaucoma care demonstrate slow rates of visual field progression. The MD rate in the current study was similar to an interventional prospective study, but considerably less negative compared to published studies with similar design. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Damage Control Resuscitation: Directly Addressing the Early Coagulopathy of Trauma

DTIC Science & Technology

2007-02-01

FACS, Jay Johannigman, MD, FS, FACS, Peter Mahoney, FRCA, RAMC , Sumeru Mehta, MD, E. Darrin Cox, MD, FACS, Michael J. Gehrke, MD, Greg J. Beilman, MD...opportunity to formally evaluate the immediate and direct treatment of the coagulopathy of trauma is available. Submitted for publication September 22, 2006...the results were not evaluated in randomized human trials.33–35 Additionally, the potential benefits of mitigating ischemia-induced reperfusion injury

MD-2 residues tyrosine 42, arginine 69, aspartic acid 122, and leucine 125 provide species specificity for lipid IVA.

PubMed

Meng, Jianmin; Drolet, Joshua R; Monks, Brian G; Golenbock, Douglas T

2010-09-03

Lipopolysaccharide (LPS) activates the innate immune response through the Toll-like receptor 4 (TLR4).MD-2 complex. A synthetic lipid A precursor, lipid IV(A), induces an innate immune response in mice but not in humans. Both TLR4 and MD-2 are required for the agonist activity of lipid IV(A) in mice, with TLR4 interacting through specific surface charges at the dimerization interface. In this study, we used site-directed mutagenesis to identify the MD-2 residues that determine lipid IV(A) species specificity. A single mutation of murine MD-2 at the hydrophobic pocket entrance, E122K, substantially reduced the response to lipid IV(A). Combining the murine MD-2 E122K with the murine TLR4 K367E/S386K/R434Q mutations completely abolished the response to lipid IV(A), effectively converting the murine cellular response to a human-like response. In human cells, however, simultaneous mutations of K122E, K125L, Y41F, and R69G on human MD-2 were required to promote a response to lipid IV(A). Combining the human MD-2 quadruple mutations with the human TLR4 E369K/Q436R mutations completely converted the human MD-2/human TLR4 receptor to a murine-like receptor. Because MD-2 residues 122 and 125 reside at the dimerization interface near the pocket entrance, surface charge differences here directly affect receptor dimerization. In comparison, residues 42 and 69 reside at the MD-2/TLR4 interaction surface opposite the dimerization interface. Surface charge differences there likely affect the binding angle and/or rigidity between MD-2 and TLR4, exerting an indirect influence on receptor dimerization and activation. Thus, surface charge differences at the two MD-2/TLR4 interfaces determine the species-specific activation of lipid IV(A).

Apple F-Box Protein MdMAX2 Regulates Plant Photomorphogenesis and Stress Response.

PubMed

An, Jian-Ping; Li, Rui; Qu, Feng-Jia; You, Chun-Xiang; Wang, Xiao-Fei; Hao, Yu-Jin

2016-01-01

MAX2 (MORE AXILLARY GROWTH2) is involved in diverse physiological processes, including photomorphogenesis, the abiotic stress response, as well as karrikin and strigolactone signaling-mediated shoot branching. In this study, MdMAX2, an F-box protein that is a homolog of Arabidopsis MAX2, was identified and characterized. Overexpression of MdMAX2 in apple calli enhanced the accumulation of anthocyanin. Ectopic expression of MdMAX2 in Arabidopsis exhibited photomorphogenesis phenotypes, including increased anthocyanin content and decreased hypocotyl length. Further study indicated that MdMAX2 might promote plant photomorphogenesis by affecting the auxin signaling as well as other plant hormones. Transcripts of MdMAX2 were noticeably up-regulated in response to NaCl and Mannitol treatments. Moreover, compared with the wild-type, the MdMAX2 -overexpressing apple calli and Arabidopsis exhibited increased tolerance to salt and drought stresses. Taken together, these results suggest that MdMAX2 plays a positive regulatory role in plant photomorphogenesis and stress response.

An apple NAC transcription factor negatively regulates cold tolerance via CBF-dependent pathway.

PubMed

An, Jian-Ping; Li, Rui; Qu, Feng-Jia; You, Chun-Xiang; Wang, Xiao-Fei; Hao, Yu-Jin

2018-02-01

Cold stress is an adverse stimulus that affects plant growth and development, and the C-repeat binding factor (CBF) cold-regulatory cascade has been regarded as a master regulator in the plant response to cold stress. Here, we showed that a NAC transcription factor modulated low-temperature tolerance. MdNAC029/MdNAP, an apple NAC gene was isolated and its role in regulating cold tolerance was investigated. MdNAC029 was responsive to low-temperature treatment, and over-expression of MdNAC029 reduced cold tolerance in apple calli and Arabidopsis. Furthermore, EMSA assays and transient expression assays demonstrated that MdNAC029 directly repressed the expression of MdCBF1 and MdCBF4 by binding to their promoters. Taken together, our data suggest that MdNAC029 functions as a negative regulator in regulating plant cold tolerance in a CBF-dependent manner, providing a deeper understanding of NAC transcription-factor-mediated cold tolerance. Copyright © 2017 Elsevier GmbH. All rights reserved.

MdHY5 positively regulates cold tolerance via CBF-dependent and CBF-independent pathways in apple.

PubMed

An, Jian-Ping; Yao, Ji-Fang; Wang, Xiao-Na; You, Chun-Xiang; Wang, Xiao-Fei; Hao, Yu-Jin

2017-11-01

Cold stress is a major external stimulator that affects crop quality and productivity. The CBF cold regulatory pathway has been regarded as a master regulator in the response to cold stress. In this study, we found that the apple bZIP transcription factor, MdHY5, was responsive to cold treatment both at the transcriptional and at the post-translational levels. Moreover, overexpression of MdHY5 enhanced cold tolerance in apple calli and Arabidopsis. Subsequently, EMSA assay and transient expression assay demonstrated that MdHY5 positively regulated the transcript of MdCBF1 by binding to G-Box motif of its promoter. Furthermore, MdHY5 also regulated the expression of CBF-independent cold-regulated genes. Taken together, our data suggest that MdHY5 positively modulates plant cold tolerance through CBF-dependent and CBF-independent pathways, providing a deeper understanding of MdHY5-regulated cold tolerance in apple. Copyright © 2017 Elsevier GmbH. All rights reserved.

Neurobiological Underpinnings of Math and Reading Learning Disabilities

PubMed Central

Ashkenazi, Sarit; Black, Jessica M.; Abrams, Daniel A.; Hoeft, Fumiko; Menon, Vinod

2013-01-01

The primary goal of this review is to highlight current research and theories describing the neurobiological basis of math (MD), reading (RD), and comorbid math and reading disability (MD+RD). We first describe the unique brain and cognitive processes involved in acquisition of math and reading skills, emphasizing similarities and differences in each domain. Next we review functional imaging studies of MD and RD in children, integrating relevant theories from experimental psychology and cognitive neuroscience to characterize the functional neuroanatomy of cognitive dysfunction in MD and RD. We then review recent research on the anatomical correlates of MD and RD. Converging evidence from morphometry and tractography studies are presented to highlight distinct patterns of white matter pathways which are disrupted in MD and RD. Finally, we examine how the intersection of MD and RD provides a unique opportunity to clarify the unique and shared brain systems which adversely impact learning and skill acquisition in MD and RD, and point out important areas for future work on comorbid learning disabilities. PMID:23572008

Tutorial: Determination of thermal boundary resistance by molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Liang, Zhi; Hu, Ming

2018-05-01

Due to the high surface-to-volume ratio of nanostructured components in microelectronics and other advanced devices, the thermal resistance at material interfaces can strongly affect the overall thermal behavior in these devices. Therefore, the thermal boundary resistance, R, must be taken into account in the thermal analysis of nanoscale structures and devices. This article is a tutorial on the determination of R and the analysis of interfacial thermal transport via molecular dynamics (MD) simulations. In addition to reviewing the commonly used equilibrium and non-equilibrium MD models for the determination of R, we also discuss several MD simulation methods which can be used to understand interfacial thermal transport behavior. To illustrate how these MD models work for various interfaces, we will show several examples of MD simulation results on thermal transport across solid-solid, solid-liquid, and solid-gas interfaces. The advantages and drawbacks of a few other MD models such as approach-to-equilibrium MD and first-principles MD are also discussed.

Clinical features of and risk factors for major depression with history of postpartum episodes in Han Chinese women: A retrospective study.

PubMed

Yang, Fuzhong; Gardner, Charles O; Bigdeli, Tim; Gao, Jingfang; Zhang, Zhen; Tao, Ming; Liu, Ying; Li, Youhui; Wang, Gang; Shi, Jianguo; Gao, Chengge; Zhang, Kerang; Li, Kan; Wang, Xumei; Liu, Lanfen; Sun, Jing; Du, Bo; Shi, Shenxun; Zhang, Jingbei; Wu, Wenyuan; Wang, Xueyi; Shen, Jianhua; Liu, Tiebang; Gu, Danhua; Liang, Wei; Deng, Hong; Pan, Jiyang; Yang, Lijun; Jian, Hu; Jiang, Guoqin; Meng, Huaqing; Miao, Guodong; Li, Yi; Hu, Chunmei; Huang, Guoping; Zhang, Yutang; Chen, Yunchun; Ha, Baowei; Gao, Shu; Fang, Xiang; Mei, Qiyi; Hong, Xiaohong; Yang, Donglin; Liu, Tieqiao; Fengyu, Yu; Zhong, Hui; Sang, Hong; Chen, Guibing; Cai, Min; Song, Yan; Dong, Jicheng; Shen, Zhenmin; Zhang, Wei; Wang, Xiaoping; Pan, Runde; Liu, Xiaojuan; Li, Yi; Liu, Zhengrong; Zhang, Qiwen; Li, Gongying; Flint, Jonathan; Kendler, Kenneth S

2015-09-01

We sought to investigate the clinical features of and risk factors for recurrent major depression (MD) with history of postpartum episodes (PPD) in Han Chinese women and the differences between first-onset postpartum MD (MD that has its first lifetime depressive episode in the postpartum period) and first-onset non-postpartum MD (MD with history of PPD and has its first lifetime depressive episode in a period other than postpartum). Data were derived from the China, Oxford and Virginia Commonwealth University Experimental Research on Genetic Epidemiology (CONVERGE) study (N=6017 cases) and analyzed in two steps. We first examined the clinical features of and risk factors for MD patients with (N=981) or without (N=4410) a history of PPD. We then compared the differences between first-onset postpartum MD (N=583) and first-onset non-postpartum MD (N=398) in those with a history of PPD. Linear, logistic and multinomial logistic models were employed to measure the associations. A history of PPD was associated with more guilt feelings, greater psychiatric comorbidity, higher neuroticism, earlier onset and more chronicity (OR 0.2-2.8). Severe premenstrual symptoms (PMS) and more childbirths increased the risk of PPD, as did a family history of MD, childhood sexual abuse, stressful life events and lack of social support (OR 1.1-1.3). In the MD with history of PPD subsample, first-onset postpartum MD was associated with fewer recurrent major depressive episodes, less psychiatric comorbidity, lower neuroticism, less severe PMS and fewer disagreements with their husbands (OR 0.5-0.8), but more childbirths (OR 1.2). Data were obtained retrospectively through interview and recall bias may have affected the results. MD with history of PPD in Han Chinese women is typically chronic and severe, with particular risk factors including severe PMS and more childbirths. First-onset postpartum MD and first-onset non-postpartum MD can be partly differentiated by their clinical features and risk factors, but are not clearly distinctive. Copyright © 2015. Published by Elsevier B.V.

The effects of the mediterranean diet on biomarkers of vascular wall inflammation and plaque vulnerability in subjects with high risk for cardiovascular disease. A randomized trial.

PubMed

Casas, Rosa; Sacanella, Emilio; Urpí-Sardà, Mireia; Chiva-Blanch, Gemma; Ros, Emilio; Martínez-González, Miguel-Angel; Covas, Maria-Isabel; Salas-Salvadó, Jordi; Fiol, Miquel; Arós, Fernando; Estruch, Ramon

2014-01-01

Adherence to the Mediterranean diet (MD) is associated with reduced morbidity and mortality due to cardiovascular disease. However, how the MD exerts its effects is not fully known. To assess the 12-month effects of two enhanced MDs compared to a low-fat diet on inflammatory biomarkers related to atherosclerosis and plaque vulnerability in a subcohort of the PREDIMED (Prevención con Dieta Mediterránea) study. A total of 164 participants at high risk for cardiovascular disease were randomized into three diet groups: MD supplemented with 50mL/d of extra virgin olive oil (MD+EVOO) or 30 g/d of nuts (MD+Nuts) and a low-fat diet. Changes in classical cardiovascular risk factors, inflammatory biomarkers of atherosclerosis and plaque vulnerability were measured after 12 months of intervention. Compared to participants in the low-fat diet group, those receiving MD+EVOO and MD+Nuts showed a higher decrease in systolic (6mmHg) and diastolic (3mmHg) blood pressure (P = 0.02; both), as well as a reduction of 10% and 8% in LDL-cholesterol (P = 0.04), respectively. Patients in the MD+Nuts group showed a significant reduction of 34% in CD40 expression on monocyte surface compared to low-fat diet patients (P = 0.03). In addition, inflammatory biomarkers related to plaque instability such as C-reactive protein and interleukin-6 were reduced by 45% and 35% and 95% and 90% in the MD+EVOO and MD+Nuts groups, respectively (P<0.05; all) compared to the low-fat diet group. Likewise, sICAM and P-selectin were also reduced by 50% and 27%, respectively in the MD+EVOO group (P = 0.04) and P-selectin by 19% in MD+Nuts group (P = 0.04) compared to the low-fat diet group. Adherence to the MD is associated with an increase in serum markers of atheroma plaque stability which may explain, at least in part, the protective role of MD against ischemic heart disease. www.controlled-trials.com ISRCTN35739639.

Logistic model analysis of neurological findings in Minamata disease and the predicting index.

PubMed

Nakagawa, Masanori; Kodama, Tomoko; Akiba, Suminori; Arimura, Kimiyoshi; Wakamiya, Junji; Futatsuka, Makoto; Kitano, Takao; Osame, Mitsuhiro

2002-01-01

To establish a statistical diagnostic method to identify patients with Minamata disease (MD) considering factors of aging and sex, we analyzed the neurological findings in MD patients, inhabitants in a methylmercury polluted (MP) area, and inhabitants in a non-MP area. We compared the neurological findings in MD patients and inhabitants aged more than 40 years in the non-MP area. Based on the different frequencies of the neurological signs in the two groups, we devised the following formula to calculate the predicting index for MD: predicting index = 1/(1+e(-x)) x 100 (The value of x was calculated using the regression coefficients of each neurological finding obtained from logistic analysis. The index 100 indicated MD, and 0, non-MD). Using this method, we found that 100% of male and 98% of female patients with MD (95 cases) gave predicting indices higher than 95. Five percent of the aged inhabitants in the MP area (598 inhabitants) and 0.2% of those in the non-MP area (558 inhabitants) gave predicting indices of 50 or higher. Our statistical diagnostic method for MD was useful in distinguishing MD patients from healthy elders based on their neurological findings.

The Structural Basis for Lipid and Endotoxin Binding in RP105-MD-1, and Consequences for Regulation of Host Lipopolysaccharide Sensitivity.

PubMed

Ortiz-Suarez, Maite L; Bond, Peter J

2016-01-05

MD-1 is a member of the MD-2-related lipid-recognition (ML) family, and associates with RP105, a cell-surface protein that resembles Toll-like receptor 4 (TLR4). The RP105⋅MD-1 complex has been proposed to play a role in fine-tuning the innate immune response to endotoxin such as bacterial lipopolysaccharide (LPS) via TLR4⋅MD-2, but controversy surrounds its mechanism. We have used atomically detailed simulations to reveal the structural basis for ligand binding and consequent functional dynamics of MD-1 and the RP105 complex. We rationalize reports of endogenous phospholipid binding, by showing that they prevent collapse of the malleable MD-1 fold, before refining crystallographic models and uncovering likely binding modes for LPS analogs. Subsequent binding affinity calculations reveal that endotoxin specificity arises from the entropic cost of expanding the MD-1 cavity to accommodate bulky lipid tails, and support the role of MD-1 as a "sink" that sequesters endotoxin from TLR4 and stabilizes RP105/TLR4 interactions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Remains of abutments for Bridge No. 1575 at MD Rt. ...

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

Remains of abutments for Bridge No. 1575 at MD Rt. 51 in Spring Gap, Maryland, looking northeast. (Compare with HAER MD-115 photos taken 1988). - Western Maryland Railway, Cumberland Extension, Pearre to North Branch, from WM milepost 125 to 160, Pearre, Washington County, MD

Why do people google movement disorders? An infodemiological study of information seeking behaviors.

PubMed

Brigo, Francesco; Erro, Roberto

2016-05-01

Millions of people worldwide everyday search Google or Wikipedia to look for health-related information. Aim of this study was to evaluate and interpret web search queries for terms related to movement disorders (MD) in English-speaking countries and their changes over time. We analyzed information regarding the volume of online searches in Google and Wikipedia for the most common MD and their treatments. We determined the highest search volume peaks to identify possible relation with online news headlines. The volume of searches for some queries related to MD entered in Google enormously increased over time. Most queries were related to definition, subtypes, symptoms and treatment (mostly to adverse effects, or alternatively, to possible alternative treatments). The highest peaks of MD search queries were temporally related to news about celebrities suffering from MD, to specific mass-media events or to news concerning pharmaceutic companies or scientific discoveries on MD. An increasing number of people use Google and Wikipedia to look for terms related to MD to obtain information on definitions, causes and symptoms, possibly to aid initial self-diagnosis. MD information demand and the actual prevalence of different MDs do not travel together: web search volume may mirrors patients' fears and worries about some particular disorders perceived as more serious than others, or may be driven by release of news about celebrities suffering from MD, "breaking news" or specific mass-media events regarding MD.

Structural and functional analyses of genes encoding VQ proteins in apple.

PubMed

Dong, Qinglong; Zhao, Shuang; Duan, Dingyue; Tian, Yi; Wang, Yanpeng; Mao, Ke; Zhou, Zongshan; Ma, Fengwang

2018-07-01

Recent studies with Arabidopsis and soybean have shown that a class of valine-glutamine (VQ) motif-containing proteins interacts with some WRKY transcription factors. However, little is known about the evolution, structures, and functions of those proteins in apple. Here, we examined their features and identified 49 apple VQ genes. Our evolutional analysis revealed that the proteins could be clustered into nine groups together with their homologues in 33 species. Historically, the main characteristics of proteins in Groups I, V, VI, VII, IX, and X were thought to have been generated before the monocot-dicot split, whereas those in Groups II, III + IV, and VIII were generated after that split. In the structural analysis, apple MdVQ proteins appeared to bind only with Group I and IIc MdWRKY proteins. Meanwhile, MdVQ1, MdVQ10, MdVQ15, and MdVQ36 interacted with multiple MdVQ proteins to form heterodimers but MdVQ15 formed a homodimer. The functional analysis indicated that overexpression of some apple MdVQs in Arabidopsis and tobacco plants effected their vegetative and reproductive growth. These results provide important information about the characteristics of apple MdVQ genes and can serve as a solid foundation for further studies about the role of WRKY-VQ interactions in regulating apple developmental and defense mechanisms. Copyright © 2018 Elsevier B.V. All rights reserved.

Malaria, Moderate to Severe Anaemia, and Malarial Anaemia in Children at Presentation to Hospital in the Mount Cameroon Area: A Cross-Sectional Study

PubMed Central

Taiwe, Germain Sotoing

2016-01-01

Background. Malaria remains a major killer of children in Sub-Saharan Africa, while anaemia is a public health problem with significant morbidity and mortality. Examining the factors associated with moderate to severe anaemia (MdSA) and malarial anaemia as well as the haematological characteristics is essential. Methodology. Children (1–14 years) at presentation at the Regional Hospital Annex-Buea were examined clinically and blood samples were collected for malaria parasite detection and full blood count evaluation. Results. Plasmodium falciparum, anaemia, and malarial anaemia occurred in 33.8%, 62.0%, and 23.6% of the 216 children, respectively. Anaemia prevalence was significantly higher in malaria parasite positive children and those with fever than their respective counterparts. MdSA and moderate to severe malarial anaemia (MdSMA) were detected in 38.0% and 15.3% of the participants, respectively. The prevalence of MdSA was significantly higher in children whose household head had no formal education, resided in the lowland, or was febrile, while MdSMA was significantly higher in febrile children only. Children with MdSMA had significantly lower mean white blood cell, lymphocyte, and platelet counts while the mean granulocyte count was significantly higher. Conclusion. Being febrile was the only predictor of both MdSA and MdSMA. More haematological insult occurred in children with MdSMA compared to MdSA. PMID:27895939

The MdTFL1 gene of apple (Malus x domestica Borkh.) reduces vegetative growth and generation time.

PubMed

Flachowsky, Henryk; Szankowski, Iris; Waidmann, Sascha; Peil, Andreas; Tränkner, Conny; Hanke, Magda-Viola

2012-10-01

TFL1 is known as a floral repressor in Arabidopsis thaliana (L.) Heynh. In apple there are two TFL1 homologs, MdTFL1-1 and MdTFL1-2. The MdTFL1-1 gene was silenced in transgenic clones expressing a hairpin gene construct of a 323 bp fragment of MdTFL1-1. The hairpin gene construct was transferred to three different apple genotypes. Of 22 transgenic clones, 21 showed a significant reduction in MdTFL1-1 mRNA expression. Precocious flowering was obtained for 20 clones, which flowered already during in vitro cultivation. Nineteen clones could successfully be transferred to the greenhouse where 18 of them flowered within a few weeks followed by the death or at least a strongly inhibited vegetative growth of the plant. Most of the transgenic flowers developed abnormally. Results obtained on greenhouse-grown plants of the transgenic clones and transgenic seedlings clearly demonstrated the major role of MdTFL1 genes in maintaining the vegetative growth as prerequisite for a perennial lifecycle. It was shown that MdTFL1 dsRNAi promotes a life history similar to annual plants. Preliminary results obtained from grafting experiments with non-transgenic scions grafted onto MdTFL1 dsRNAi transgenic rootstocks indicated that the flower-inducing signal obtained after silencing of MdTFL1 genes seems not to be graft-transmissible.

Evidence for ProTα-TLR4/MD-2 binding: molecular dynamics and gravimetric assay studies.

PubMed

Omotuyi, Olaposi; Matsunaga, Hayato; Ueda, Hiroshi

2015-01-01

During preconditioning, lipopolysaccharide (LPS) selectively activates TLR4/MD-2/Toll/IL-1 receptor-domain-containing adaptor inducing IFN-β (TRIF) pathway instead of pro-inflammatory myeloid differentiation protein-88 (MyD88)/MyD88-adaptor-like protein (MAL) pathway. Extracellular prothymosin alpha (ProTα) is also known to selectively activate the TLR4/MD2/TRIF-IRF3 pathway in certain diseased conditions. In the current study, biophysical evidence for ProTα/TLR4/MD-2 complex formation and its interaction dynamics have been studied. Gravimetric assay was used to investigate ProTα/TLR4/MD-2 complex formation while molecular dynamics (MD) simulation was used to study its interaction dynamics. Through electrostatic interaction, full-length ProTα (F-ProTα) C-terminal peptide (aa 91 - 111) superficially interacts with similar TLR4/MD-2 (KD = 273.36 nm vs 16.07 μg/ml [LPS]) conformation with LPS at an overlapping three-dimensional space while F-ProTα is hinged to the TLR4 scaffold by one-amino acid shift-Mosoian domain (aa-51 - 90). Comparatively, F-ProTα better stabilizes MD-2 metastable states transition and mediates higher TLR4/MD-2 interaction than LPS. ProTα via its C-terminal peptide (aa 91 - 111) exhibits in vitro biophysical contact with TLR4/MD-2 complex conformation recognized by LPS at overlapping LPS-binding positions.

Enhanced conformational sampling of nucleic acids by a new Hamiltonian replica exchange molecular dynamics approach.

PubMed

Curuksu, Jeremy; Zacharias, Martin

2009-03-14

Although molecular dynamics (MD) simulations have been applied frequently to study flexible molecules, the sampling of conformational states separated by barriers is limited due to currently possible simulation time scales. Replica-exchange (Rex)MD simulations that allow for exchanges between simulations performed at different temperatures (T-RexMD) can achieve improved conformational sampling. However, in the case of T-RexMD the computational demand grows rapidly with system size. A Hamiltonian RexMD method that specifically enhances coupled dihedral angle transitions has been developed. The method employs added biasing potentials as replica parameters that destabilize available dihedral substates and was applied to study coupled dihedral transitions in nucleic acid molecules. The biasing potentials can be either fixed at the beginning of the simulation or optimized during an equilibration phase. The method was extensively tested and compared to conventional MD simulations and T-RexMD simulations on an adenine dinucleotide system and on a DNA abasic site. The biasing potential RexMD method showed improved sampling of conformational substates compared to conventional MD simulations similar to T-RexMD simulations but at a fraction of the computational demand. It is well suited to study systematically the fine structure and dynamics of large nucleic acids under realistic conditions including explicit solvent and ions and can be easily extended to other types of molecules.

Experience-enabled enhancement of adult visual cortex function.

PubMed

Tschetter, Wayne W; Alam, Nazia M; Yee, Christopher W; Gorz, Mario; Douglas, Robert M; Sagdullaev, Botir; Prusky, Glen T

2013-03-20

We previously reported in adult mice that visuomotor experience during monocular deprivation (MD) augmented enhancement of visual-cortex-dependent behavior through the non-deprived eye (NDE) during deprivation, and enabled enhanced function to persist after MD. We investigated the physiological substrates of this experience-enabled form of adult cortical plasticity by measuring visual behavior and visually evoked potentials (VEPs) in binocular visual cortex of the same mice before, during, and after MD. MD on its own potentiated VEPs contralateral to the NDE during MD and shifted ocular dominance (OD) in favor of the NDE in both hemispheres. Whereas we expected visuomotor experience during MD to augment these effects, instead enhanced responses contralateral to the NDE, and the OD shift ipsilateral to the NDE were attenuated. However, in the same animals, we measured NMDA receptor-dependent VEP potentiation ipsilateral to the NDE during MD, which persisted after MD. The results indicate that visuomotor experience during adult MD leads to enduring enhancement of behavioral function, not simply by amplifying MD-induced changes in cortical OD, but through an independent process of increasing NDE drive in ipsilateral visual cortex. Because the plasticity is resident in the mature visual cortex and selectively effects gain of visual behavior through experiential means, it may have the therapeutic potential to target and non-invasively treat eye- or visual-field-specific cortical impairment.

Comparison of mean deviation with AGIS and CIGTS scores in association with structural parameters in glaucomatous eyes.

PubMed

Naka, Maiko; Kanamori, Akiyasu; Tatsumi, Yasuko; Fujioka, Miyuki; Nagai-Kusuhara, Azusa; Nakamura, Makoto; Negi, Akira

2009-01-01

To evaluate which of the 3 clinically used visual field indices including mean deviation (MD), Advanced Glaucoma Intervention Study (AGIS) score, and Collaborative Initial Glaucoma Treatment Study (CIGTS) score are best in evaluating functional damage of glaucomatous optic neuropathy. In 213 glaucomatous eyes, peripapillary retinal nerve fiber layer thickness (RNFLT) and optic disc configuration were measured with Stratus optical coherence tomography and Heidelberg Retina Tomograph-2, respectively. Visual field was measured with standard automated perimetry 30-2. Correlations of the structural parameters compared with the 3 VF indices using second polynomial regression were calculated. In addition, these correlations were analyzed among eyes of 3 different stages of glaucoma, as defined by MD score (early, MD> or =-6 dB; moderate, -12 dB< or =MD<-6 dB; advanced, MD<-12 dB). Among structure-function relationships in all subjects, the highest correlation determination (R) was MD with RNFLT (=0.298). CIGTS score showed better R than MD or AGIS score with rim area, but these values were not higher than any R with RNFLT. In analyses of 3 groups depending on MD, statistically significant structure-function correlations were observed only in patients with an advanced stage. No clear difference was found among MD and AGIS/CIGTS scores in expressing functional damage of glaucomatous eyes. MD is suggested to be no worse than others in monitoring glaucoma in clinical setting.

Do word-problem features differentially affect problem difficulty as a function of students' mathematics difficulty with and without reading difficulty?

PubMed

Powell, Sarah R; Fuchs, Lynn S; Fuchs, Douglas; Cirino, Paul T; Fletcher, Jack M

2009-01-01

This study examined whether and, if so, how word-problem features differentially affect problem difficulty as a function of mathematics difficulty (MD) status: no MD (n = 109), MD only (n = 109), or MD in combination with reading difficulties (MDRD; n = 109). The problem features were problem type (total, difference, or change) and position of missing information in the number sentence representing the word problem (first, second, or third position). Students were assessed on 14 word problems near the beginning of third grade. Consistent with the hypothesis that mathematical cognition differs as a function of MD subtype, problem type affected problem difficulty differentially for MDRD versus MD-only students; however, the position of missing information in word problems did not. Implications for MD subtyping and for instruction are discussed.

Reconfigurable Flight Control System for a STOL (Short Take-Off and Landing) Aircraft Using Quantitative Feedback Theory.

DTIC Science & Technology

1984-12-01

XD2, XD3, XD4, XD5, XD6, XD7, XDS, 7M1, MA, MH, M0,MU, MDl,MD2, MD3, MD4, M5, MOS, MD7, MDS REAL CNB, CYB, CL, L, N DIMENSION AMAT(4,4), BMAT (4,S...NO, MU, ND1, MD2, ND3, MD4,ND5, MD6, ND7, NO REAL CNB, CYB, CL, L, N DIMENSION AMAT(4,4), BMAT (4,S)V DIMENSION DIRMAT(5, 5) ,DIRBMAT(5, SJ CHARACTER*3...INPUT MATRIX 8 C BMAT (l,1) - XO1 BMAT (1,2) - X02 BMAT (1,3) = XD3 BMAT (1,4) -XO4 SMAT(1,5) -XD5 BMAT (1,&) - XDG BMQT(1,7) = XD7 EMAT(I,8) - XDB BMAT (,1

The cold-induced basic helix-loop-helix transcription factor gene MdCIbHLH1 encodes an ICE-like protein in apple

PubMed Central

2012-01-01

Background Plant growth is greatly affected by low temperatures, and the expression of a number of genes is induced by cold stress. Although many genes in the cold signaling pathway have been identified in Arabidopsis, little is known about the transcription factors involved in the cold stress response in apple. Results Here, we show that the apple bHLH (basic helix-loop-helix) gene MdCIbHLH1 (Cold-Induced bHLH1), which encodes an ICE-like protein, was noticeably induced in response to cold stress. The MdCIbHLH1 protein specifically bound to the MYC recognition sequences in the AtCBF3 promoter, and MdCIbHLH1 overexpression enhanced cold tolerance in transgenic Arabidopsis. In addition, the MdCIbHLH1 protein bound to the promoters of MdCBF2 and favorably contributed to cold tolerance in transgenic apple plants by upregulating the expression of MdCBF2 through the CBF (C-repeat-binding factor) pathway. Our findings indicate that MdCIbHLH1 functions in stress tolerance in different species. For example, ectopic MdCIbHLH1 expression conferred enhanced chilling tolerance in transgenic tobacco. Finally, we observed that cold induces the degradation of the MdCIbHLH1 protein in apple and that this degradation was potentially mediated by ubiquitination and sumoylation. Conclusions Based on these findings, MdCIbHLH1 encodes a transcription factor that is important for the cold tolerance response in apple. PMID:22336381

Mediodorsal Thalamic Neurons Mirror the Activity of Medial Prefrontal Neurons Responding to Movement and Reinforcement during a Dynamic DNMTP Task

PubMed Central

Miller, Rikki L.A.

2017-01-01

Abstract The mediodorsal nucleus (MD) interacts with medial prefrontal cortex (mPFC) to support learning and adaptive decision-making. MD receives driver (layer 5) and modulatory (layer 6) projections from PFC and is the main source of driver thalamic projections to middle cortical layers of PFC. Little is known about the activity of MD neurons and their influence on PFC during decision-making. We recorded MD neurons in rats performing a dynamic delayed nonmatching to position (dDNMTP) task and compared results to a previous study of mPFC with the same task (Onos et al., 2016). Criterion event-related responses were observed for 22% (254/1179) of neurons recorded in MD, 237 (93%) of which exhibited activity consistent with mPFC response types. More MD than mPFC neurons exhibited responses related to movement (45% vs. 29%) and reinforcement (51% vs. 27%). MD had few responses related to lever presses, and none related to preparation or memory delay, which constituted 43% of event-related activity in mPFC. Comparison of averaged normalized population activity and population response times confirmed the broad similarity of common response types in MD and mPFC and revealed differences in the onset and offset of some response types. Our results show that MD represents information about actions and outcomes essential for decision-making during dDNMTP, consistent with evidence from lesion studies that MD supports reward-based learning and action-selection. These findings support the hypothesis that MD reinforces task-relevant neural activity in PFC that gives rise to adaptive behavior. PMID:29034318

Mediodorsal Thalamic Neurons Mirror the Activity of Medial Prefrontal Neurons Responding to Movement and Reinforcement during a Dynamic DNMTP Task.

PubMed

Miller, Rikki L A; Francoeur, Miranda J; Gibson, Brett M; Mair, Robert G

2017-01-01

The mediodorsal nucleus (MD) interacts with medial prefrontal cortex (mPFC) to support learning and adaptive decision-making. MD receives driver (layer 5) and modulatory (layer 6) projections from PFC and is the main source of driver thalamic projections to middle cortical layers of PFC. Little is known about the activity of MD neurons and their influence on PFC during decision-making. We recorded MD neurons in rats performing a dynamic delayed nonmatching to position (dDNMTP) task and compared results to a previous study of mPFC with the same task (Onos et al., 2016). Criterion event-related responses were observed for 22% (254/1179) of neurons recorded in MD, 237 (93%) of which exhibited activity consistent with mPFC response types. More MD than mPFC neurons exhibited responses related to movement (45% vs. 29%) and reinforcement (51% vs. 27%). MD had few responses related to lever presses, and none related to preparation or memory delay, which constituted 43% of event-related activity in mPFC. Comparison of averaged normalized population activity and population response times confirmed the broad similarity of common response types in MD and mPFC and revealed differences in the onset and offset of some response types. Our results show that MD represents information about actions and outcomes essential for decision-making during dDNMTP, consistent with evidence from lesion studies that MD supports reward-based learning and action-selection. These findings support the hypothesis that MD reinforces task-relevant neural activity in PFC that gives rise to adaptive behavior.

The knock-down of the expression of MdMLO19 reduces susceptibility to powdery mildew (Podosphaera leucotricha) in apple (Malus domestica).

PubMed

Pessina, Stefano; Angeli, Dario; Martens, Stefan; Visser, Richard G F; Bai, Yuling; Salamini, Francesco; Velasco, Riccardo; Schouten, Henk J; Malnoy, Mickael

2016-10-01

Varieties resistant to powdery mildew (PM; caused by Podosphaera leucotricha) are a major component of sustainable apple production. Resistance can be achieved by knocking-out susceptibility S-genes to be singled out among members of the MLO (Mildew Locus O) gene family. Candidates are MLO S-genes of phylogenetic clade V up-regulated upon PM inoculation, such as MdMLO11 and 19 (clade V) and MdMLO18 (clade VII). We report the knock-down through RNA interference of MdMLO11 and 19, as well as the complementation of resistance with MdMLO18 in the Arabidopsis thaliana triple mlo mutant Atmlo2/6/12. The knock-down of MdMLO19 reduced PM disease severity by 75%, whereas the knock-down of MdMLO11, alone or in combination with MdMLO19, did not result in any reduction or additional reduction of susceptibility compared with MdMLO19 alone. The test in A. thaliana excluded a role for MdMLO18 in PM susceptibility. Cell wall appositions (papillae) were present in both PM-resistant and PM-susceptible plants, but were larger in resistant lines. No obvious negative phenotype was observed in plants with mlo genes knocked down. Apparently, MdMLO19 plays the pivotal role in apple PM susceptibility and its knock-down induces a very significant level of resistance. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Studies of the TLR4-associated protein MD-2 using yeast-display and mutational analyses

PubMed Central

Mattis, Daiva M.; Chervin, Adam; Ranoa, Diana; Kelley, Stacy; Tapping, Richard; Kranz, David M.

2015-01-01

Bacterial lipopolysaccharide (LPS) activates the innate immune system by forming a complex with myeloid differentiation factor 2 (MD-2) and Toll-like receptor 4 (TLR4), which is present on antigen presenting cells. MD-2 plays an essential role in this activation of the innate immune system as a member of the ternary complex, TLR4:MD-2:LPS. With the goal of further understanding the molecular details of the interaction of MD-2 with LPS and TLR4, and possibly toward engineering dominant negative regulators of the MD-2 protein, here we subjected MD-2 to a mutational analysis using yeast display. The approach included generation of site-directed alanine mutants, and ligand-driven selections of MD-2 mutant libraries. Our findings showed that: 1) proline mutations in the F119-K132 loop that binds LPS were strongly selected for enhanced yeast surface stability, 2) there was a preference for positive-charged side chains (R/K) at residue 120 for LPS binding, and negative-charged side chains (D/E) for TLR4 binding, 3) aromatic residues were strongly preferred at F119 and F121 for LPS binding, and 4) an MD-2 mutant (T84N/D101A/S118A/S120D/K122P) exhibited increased binding to TLR4 but decreased binding to LPS. These studies revealed the impact of specific residues and regions of MD-2 on the binding of LPS and TLR4, and they provide a framework for further directed evolution of the MD-2 protein. PMID:26320630

Species-Specific Activation of TLR4 by Hypoacylated Endotoxins Governed by Residues 82 and 122 of MD-2

PubMed Central

Oblak, Alja; Jerala, Roman

2014-01-01

The Toll-like receptor 4/MD-2 receptor complex recognizes endotoxin, a Gram-negative bacterial cell envelope component. Recognition of the most potent hexaacylated form of endotoxin is mediated by the sixth acyl chain that protrudes from the MD-2 hydrophobic pocket and bridges TLR4/MD-2 to the neighboring TLR4 ectodomain, driving receptor dimerization via hydrophobic interactions. In hypoacylated endotoxins all acyl chains could be accommodated within the binding pocket of the human hMD-2. Nevertheless, tetra- and pentaacylated endotoxins activate the TLR4/MD-2 receptor of several species. We observed that amino acid residues 82 and 122, located at the entrance to the endotoxin binding site of MD-2, have major influence on the species-specific endotoxin recognition. We show that substitution of hMD-2 residue V82 with an amino acid residue with a bulkier hydrophobic side chain enables activation of TLR4/MD-2 by pentaacylated and tetraacylated endotoxins. Interaction of the lipid A phosphate group with the amino acid residue 122 of MD-2 facilitates the appropriate positioning of the hypoacylated endotoxin. Moreover, mouse TLR4 contributes to the agonistic effect of pentaacylated msbB endotoxin. We propose a molecular model that explains how the molecular differences between the murine or equine MD-2, which both have sufficiently large hydrophobic pockets to accommodate all five or four acyl chains, influence the positioning of endotoxin so that one of the acyl chains remains outside the pocket and enables hydrophobic interactions with TLR4, leading to receptor activation. PMID:25203747

Species-specific activation of TLR4 by hypoacylated endotoxins governed by residues 82 and 122 of MD-2.

PubMed

Oblak, Alja; Jerala, Roman

2014-01-01

The Toll-like receptor 4/MD-2 receptor complex recognizes endotoxin, a Gram-negative bacterial cell envelope component. Recognition of the most potent hexaacylated form of endotoxin is mediated by the sixth acyl chain that protrudes from the MD-2 hydrophobic pocket and bridges TLR4/MD-2 to the neighboring TLR4 ectodomain, driving receptor dimerization via hydrophobic interactions. In hypoacylated endotoxins all acyl chains could be accommodated within the binding pocket of the human hMD-2. Nevertheless, tetra- and pentaacylated endotoxins activate the TLR4/MD-2 receptor of several species. We observed that amino acid residues 82 and 122, located at the entrance to the endotoxin binding site of MD-2, have major influence on the species-specific endotoxin recognition. We show that substitution of hMD-2 residue V82 with an amino acid residue with a bulkier hydrophobic side chain enables activation of TLR4/MD-2 by pentaacylated and tetraacylated endotoxins. Interaction of the lipid A phosphate group with the amino acid residue 122 of MD-2 facilitates the appropriate positioning of the hypoacylated endotoxin. Moreover, mouse TLR4 contributes to the agonistic effect of pentaacylated msbB endotoxin. We propose a molecular model that explains how the molecular differences between the murine or equine MD-2, which both have sufficiently large hydrophobic pockets to accommodate all five or four acyl chains, influence the positioning of endotoxin so that one of the acyl chains remains outside the pocket and enables hydrophobic interactions with TLR4, leading to receptor activation.

75 FR 11563 - Jovencio L. Raneses, M.D.; Denial of Application

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2010-03-11

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Jovencio L. Raneses, M.D.; Denial of... Enforcement Administration, issued an Order to Show Cause to Jovencio L. Raneses, M.D. (Respondent), of San... issued by the Medical Board of California. See In re Jovencio L. Raneses, M.D., Default Decision and...

76 FR 51424 - Satinder Dang, M.D.; Revocation of Registration

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77 FR 67673 - Fernando Valle, M.D.; Decision and Order

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-13

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Studies of Tissue Perfusion Failure at LAC+USCMC and the Incorporation of the Results into a National Trauma Database

DTIC Science & Technology

2005-04-01

Context Link] 29. Gibson JG, Seligman AM, Peacock WC, et al: The circulating red cell and plasma volume and the distribution of blood in large and...BS; Gandhi, Ashutosh BS; Chien, Li-Chien MD; Lu, Kevin MD; Martin, Matthew J. MD; Chan, Linda S. PhD; Demetriades, Demetrios MD, PhD; Ahmadpour...Physicians Outcome Prediction of Emergency Patients by Noninvasive Hemodynamic Monitoring* William C. Shoemaker, MD; Charles C. J. Wo, BS; Linda

Developmental Precursors of Moral Disengagement and the Role of Moral Disengagement in the Development of Antisocial Behavior

PubMed Central

Shaw, Daniel S.; Moilanen, Kristin L.

2010-01-01

The purpose of the study was to advance our understanding of the developmental precursors of Moral Disengagement (MD) and the role of MD in the development of antisocial behavior from early risk among an ethnically diverse sample of 187 low-income boys followed prospectively from ages 1.5 to 17. Results indicated associations between early rejecting parenting, neighborhood impoverishment, and child empathy and later MD. The link between some of these early constructs and later antisocial behavior was mediated by MD. Finally, in an exploratory path model both MD and biases in social information processing were found to mediate separate paths from early risk factors to later antisocial behavior. Results were partially consistent with the notion that adolescent MD was predicted by a combination of early family, neighborhood, and child risk factors, and that MD may be a mechanism underlying some boys' risk of antisocial behavior. PMID:19777337

Eating disorders and major depression: role of anger and personality.

PubMed

Giovanni, Abbate-Daga; Carla, Gramaglia; Enrica, Marzola; Federico, Amianto; Maria, Zuccolin; Secondo, Fassino

2011-01-01

This study aimed to evaluate comorbidity for MD in a large ED sample and both personality and anger as clinical characteristics of patients with ED and MD. We assessed 838 ED patients with psychiatric evaluations and psychometric questionnaires: Temperament and Character Inventory, Eating Disorder Inventory-2, Beck Depression Inventory, and State-Trait Anger Expression Inventory. 19.5% of ED patients were found to suffer from comorbid MD and 48.7% reported clinically significant depressive symptomatology: patients with Anorexia Binge-Purging and Bulimia Nervosa were more likely to be diagnosed with MD. Irritable mood was found in the 73% of patients with MD. High Harm Avoidance (HA) and low Self-Directedness (SD) predicted MD independently of severity of the ED symptomatology, several clinical variables, and ED diagnosis. Assessing both personality and depressive symptoms could be useful to provide effective treatments. Longitudinal studies are needed to investigate the pathogenetic role of HA and SD for ED and MD.

Nerve and muscle involvement in mitochondrial disorders: an electrophysiological study.

PubMed

Mancuso, Michelangelo; Piazza, Selina; Volpi, Leda; Orsucci, Daniele; Calsolaro, Valeria; Caldarazzo Ienco, Elena; Carlesi, Cecilia; Rocchi, Anna; Petrozzi, Lucia; Calabrese, Rosanna; Siciliano, Gabriele

2012-04-01

Involvement of the peripheral nervous system in mitochondrial disorders (MD) has been previously reported. However, the exact prevalence of peripheral neuropathy and/or myopathy in MD is still unclear. In order to evaluate the prevalence of neuropathy and myopathy in MD, we performed sensory and motor nerve conduction studies (NCS) and concentric needle electromyography (EMG) in 44 unselected MD patients. NCS were abnormal in 36.4% of cases, and were consistent with a sensori-motor axonal multineuropathy (multifocal neuropathy), mainly affecting the lower limbs. EMG evidence of myopathy was present in 54.5% of patients, again mainly affecting the lower limbs. Nerve and muscle involvement was frequently subclinical. Peripheral nerve and muscle involvement is common in MD patients. Our study supports the variability of the clinical expression of MD. Further studies are needed to better understand the molecular basis underlying the phenotypic variability among MD patients.

76 FR 48898 - Robert Leigh Kale, M.D., Decision and Order

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-09

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78 FR 52802 - Tin T. Win, M.D., Dismissal of Proceeding

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2013-08-26

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75 FR 8749 - Dwayne LaFrantz Wilson, M.D.; Revocation of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

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76 FR 5686 - Drawbridge Operation Regulation; Pocomoke River, Pocomoke City, MD

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2011-02-02

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2013-02-04

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Multiscale molecular dynamics simulations of rotary motor proteins.

PubMed

Ekimoto, Toru; Ikeguchi, Mitsunori

2018-04-01

Protein functions require specific structures frequently coupled with conformational changes. The scale of the structural dynamics of proteins spans from the atomic to the molecular level. Theoretically, all-atom molecular dynamics (MD) simulation is a powerful tool to investigate protein dynamics because the MD simulation is capable of capturing conformational changes obeying the intrinsically structural features. However, to study long-timescale dynamics, efficient sampling techniques and coarse-grained (CG) approaches coupled with all-atom MD simulations, termed multiscale MD simulations, are required to overcome the timescale limitation in all-atom MD simulations. Here, we review two examples of rotary motor proteins examined using free energy landscape (FEL) analysis and CG-MD simulations. In the FEL analysis, FEL is calculated as a function of reaction coordinates, and the long-timescale dynamics corresponding to conformational changes is described as transitions on the FEL surface. Another approach is the utilization of the CG model, in which the CG parameters are tuned using the fluctuation matching methodology with all-atom MD simulations. The long-timespan dynamics is then elucidated straightforwardly by using CG-MD simulations.

Torsion of Meckel's Diverticulum in a Child

PubMed Central

Nose, Satoko; Okuyama, Hiroomi; Sasaki, Takashi; Nishimura, Mika

2013-01-01

Meckel's diverticulum (MD) is a common congenital anomaly of the gastrointestinal tract, the majority of cases of which are clinically silent. Patients with asymptomatic MD can unexpectedly develop acute abdominal pain. Making a diagnosis of MD is often difficult due to the lack of specific symptoms caused by this condition. Diagnostic laparotomy can be useful for making an accurate and prompt diagnosis of complicated MD. We herein describe a pediatric case of torsion of a MD in whom we performed laparoscopic-assisted emergency surgery. The patient was an 11-year-old male who developed sudden severe right lower abdominal pain. Clinical and laboratory findings were suggestive of appendicitis, however computed tomography scans showed a large cystic mass in the pelvis. Exploratory laparoscopy led to a diagnosis of torsion of a MD, and wedge resection of the gangrenous MD was performed through an umbilical port incision. The patient's postoperative course was uneventful. We conclude that diagnostic laparoscopy followed by laparoscopy-assisted Meckel's diverticulectomy via an umbilical incision is useful in the treatment of acute abdomen caused by MD. PMID:23466748

Symptomatic Meckel's diverticulum in newborn: two interesting additional cases and review of literature.

PubMed

Bertozzi, Mirko; Melissa, Berardino; Radicioni, Maurizio; Magrini, Elisa; Appignani, Antonino

2013-09-01

This study aimed to review the literature about symptomatic Meckel's diverticulum (MD) in the neonatal period with 2 additional uncommon cases. The authors describe 2 interesting neonatal cases of symptomatic MD and analyze the literature on this topic, with particular reference to the prevalence of sex, age at presentation, most common signs and symptoms, treatment, histology, associated anomalies, and outcome. The first patient was a term newborn with bowel obstruction by a pseudocystic MD. The second patient was a preterm infant with double perforation of the MD and ileum. Literature search for published case reports and case series on this topic reveals only 18 cases of neonatal symptomatic MD. Males are more frequently involved than females, and even preterm infants may be affected. Bowel obstruction (58.3%) and pneumoperitoneum (33.3%) are the most frequent clinical manifestation. Acute inflammation of the MD is the prominent histopathological finding (75%), although it does not seem to be related with the presence of heterotopic tissue within the MD. Surgical treatment is essential. The association of neonatal symptomatic MD with other anomalies is exceptional but is otherwise life threatening despite surgery. Bowel obstruction and pneumoperitoneum are the most frequent clinical manifestations of symptomatic MD in the newborn. Surgery is required for a definitive diagnosis and successful outcome.

Characterization of three chalcone synthase-like genes from apple (Malus x domestica Borkh.).

PubMed

Yahyaa, Mosaab; Ali, Samah; Davidovich-Rikanati, Rachel; Ibdah, Muhammad; Shachtier, Alona; Eyal, Yoram; Lewinsohn, Efraim; Ibdah, Mwafaq

2017-08-01

Apple (Malus x domestica Brokh.) is a widely cultivated deciduous tree species of significant economic importance. Apple leaves accumulate high levels of flavonoids and dihydrochalcones, and their formation is dependent on enzymes of the chalcone synthase family. Three CHS genes were cloned from apple leaves and expressed in Escherichia coli. The encoded recombinant enzymes were purified and functionally characterized. In-vitro activity assays indicated that MdCHS1, MdCHS2 and MdCHS3 code for proteins exhibiting polyketide synthase activity that accepted either p-dihydrocoumaroyl-CoA, p-coumaroyl-CoA, or cinnamoyl-CoA as starter CoA substrates in the presence of malonyl-CoA, leading to production of phloretin, naringenin chalcone, and pinocembrin chalcone. MdCHS3 coded a chalcone-dihydrochalcone synthase enzyme with narrower substrate specificity than the previous ones. The apparent Km values of MdCHS3 for p-dihydrocoumaryl-CoA and p-coumaryl-CoA were both 5.0 μM. Expression analyses of MdCHS genes varied according to tissue type. MdCHS1, MdCHS2 and MdCHS3 expression levels were associated with the levels of phloretin accumulate in the respective tissues. Copyright © 2017 Elsevier Ltd. All rights reserved.

Incidental finding of carcinoid tumor on Meckel’s diverticulum: case report and literature review, should prophylactic resection be recommended?

PubMed Central

2014-01-01

Meckel’s diverticulum (MD) is the most common congenital anomaly of the gastrointestinal tract and is caused by incomplete obliteration of the vitelline duct during intrauterine life. MD affects less than 2% of the population. In most cases, MD is asymptomatic and the estimated average complication risk of MD carriers, which is inversely proportional to age, ranges between 2% and 4%. The most common MD-related complications are gastrointestinal bleeding, intestinal obstruction and acute phlogosis. Excision is mandatory in the case of symptomatic diverticula regardless of age, while surgical treatment for asymptomatic diverticula remains controversial. According to the majority of studies, the incidental finding of MD in children is an indication for surgical resection, while the management of adults is not yet unanimous. In this case report, we describe the prophylactic resection of an incidentally detected MD, which led to the removal of an occult mucosal carcinoid tumor. In literature, the association of MD and carcinoid tumor is reported as a rare finding. Even though the strategy for adult patients of an incidental finding of MD during surgery performed for other reasons divides the experts, we recommend prophylactic excision in order to avoid any further risk. PMID:24884768

Comorbidity between reading disability and math disability: concurrent psychopathology, functional impairment, and neuropsychological functioning.

PubMed

Willcutt, Erik G; Petrill, Stephen A; Wu, Sarah; Boada, Richard; Defries, John C; Olson, Richard K; Pennington, Bruce F

2013-01-01

Reading disability (RD) and math disability (MD) frequently co-occur, but the etiology of this comorbidity is not well understood. Groups with RD only (N = 241), MD only (N = 183), and RD + MD (N = 188) and a control group with neither disorder (N = 411) completed a battery of measures of internalizing and externalizing psychopathology, social and academic functioning, and 10 neuropsychological processes. Groups with RD only, MD only, and RD + MD were significantly impaired versus the control group on nearly all measures, and the group with RD + MD was more impaired than the groups with MD and RD alone on measures of internalizing psychopathology, academic functioning, and 7 of 10 neuropsychological constructs. Multiple regression analyses of the neuropsychological measures indicated that deficits in reading and math were associated with shared weaknesses in working memory, processing speed, and verbal comprehension. In contrast, reading difficulties were uniquely associated with weaknesses in phoneme awareness and naming speed, and math deficits were uniquely associated with weaknesses in set shifting. These results support multiple-deficit neuropsychological models of RD and MD and suggest that RD and MD are distinct but related disorders that co-occur because of shared neuropsychological weaknesses in working memory, processing speed, and verbal comprehension.

Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross-sectional study with cluster analysis.

PubMed

Frejo, L; Martin-Sanz, E; Teggi, R; Trinidad, G; Soto-Varela, A; Santos-Perez, S; Manrique, R; Perez, N; Aran, I; Almeida-Branco, M S; Batuecas-Caletrio, A; Fraile, J; Espinosa-Sanchez, J M; Perez-Guillen, V; Perez-Garrigues, H; Oliva-Dominguez, M; Aleman, O; Benitez, J; Perez, P; Lopez-Escamez, J A

2017-12-01

To define clinical subgroups by cluster analysis in patients with unilateral Meniere disease (MD) and to compare them with the clinical subgroups found in bilateral MD. A cross-sectional study with a two-step cluster analysis. A tertiary referral multicenter study. Nine hundred and eighty-eight adult patients with unilateral MD. best predictors to define clinical subgroups with potential different aetiologies. We established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder (AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni- and bilateral MD. Cluster analysis defines clinical subgroups in MD, and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomised clinical trials. © 2017 John Wiley & Sons Ltd.

Humanized TLR4/MD-2 mice reveal LPS recognition differentially impacts susceptibility to Yersinia pestis and Salmonella enterica.

PubMed

Hajjar, Adeline M; Ernst, Robert K; Fortuno, Edgardo S; Brasfield, Alicia S; Yam, Cathy S; Newlon, Lindsay A; Kollmann, Tobias R; Miller, Samuel I; Wilson, Christopher B

2012-01-01

Although lipopolysaccharide (LPS) stimulation through the Toll-like receptor (TLR)-4/MD-2 receptor complex activates host defense against Gram-negative bacterial pathogens, how species-specific differences in LPS recognition impact host defense remains undefined. Herein, we establish how temperature dependent shifts in the lipid A of Yersinia pestis LPS that differentially impact recognition by mouse versus human TLR4/MD-2 dictate infection susceptibility. When grown at 37°C, Y. pestis LPS is hypo-acylated and less stimulatory to human compared with murine TLR4/MD-2. By contrast, when grown at reduced temperatures, Y. pestis LPS is more acylated, and stimulates cells equally via human and mouse TLR4/MD-2. To investigate how these temperature dependent shifts in LPS impact infection susceptibility, transgenic mice expressing human rather than mouse TLR4/MD-2 were generated. We found the increased susceptibility to Y. pestis for "humanized" TLR4/MD-2 mice directly paralleled blunted inflammatory cytokine production in response to stimulation with purified LPS. By contrast, for other Gram-negative pathogens with highly acylated lipid A including Salmonella enterica or Escherichia coli, infection susceptibility and the response after stimulation with LPS were indistinguishable between mice expressing human or mouse TLR4/MD-2. Thus, Y. pestis exploits temperature-dependent shifts in LPS acylation to selectively evade recognition by human TLR4/MD-2 uncovered with "humanized" TLR4/MD-2 transgenic mice.

Identification of two novel mammographic density loci at 6Q25.1.

PubMed

Brand, Judith S; Li, Jingmei; Humphreys, Keith; Karlsson, Robert; Eriksson, Mikael; Ivansson, Emma; Hall, Per; Czene, Kamila

2015-06-03

Mammographic density (MD) is a strong heritable and intermediate phenotype for breast cancer, but much of its genetic variation remains unexplained. We performed a large-scale genetic association study including 8,419 women of European ancestry to identify MD loci. Participants of three Swedish studies were genotyped on a custom Illumina iSelect genotyping array and percent and absolute mammographic density were ascertained using semiautomated and fully automated methods from film and digital mammograms. Linear regression analysis was used to test for SNP-MD associations, adjusting for age, body mass index, menopausal status and six principal components. Meta-analyses were performed by combining P values taking sample size, study-specific inflation factor and direction of effect into account. Genome-wide significant associations were observed for two previously identified loci: ZNF365 (rs10995194, P = 2.3 × 10(-8) for percent MD and P = 8.7 × 10(-9) for absolute MD) and AREG (rs10034692, P = 6.7 × 10(-9) for absolute MD). In addition, we found evidence of association for two variants at 6q25.1, both of which are known breast cancer susceptibility loci: rs9485370 in the TAB2 gene (P = 4.8 × 10(-9) for percent MD and P = 2.5 × 10(-8) for absolute MD) and rs60705924 in the CCDC170/ESR1 region (P = 2.2 × 10(-8) for absolute MD). Both regions have been implicated in estrogen receptor signaling with TAB2 being a potential regulator of tamoxifen response. We identified two novel MD loci at 6q25.1. These findings underscore the importance of 6q25.1 as a susceptibility region and provide more insight into the mechanisms through which MD influences breast cancer risk.

In silico analysis of the polygalacturonase inhibiting protein 1 from apple, Malus domestica.

PubMed

Matsaunyane, Lerato Bt; Oelofse, Dean; Dubery, Ian A

2015-03-11

The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. DQ185063). The gene was used to transform tobacco and potato for enhanced resistance against fungal diseases. Analysis of the MdPGIP1 nucleotide sequence revealed that the gene comprises 993 nucleotides that encode a 330 amino acid polypeptide. In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. The hydropathic evaluation of MdPGIP1 indicated a repetitive hydrophobic motif in the LRR domain and a hydrophilic surface area consistent with a globular protein. The typical consensus glycosylation sequence of Asn-X-Ser/Thr was identified in MdPGIP1, indicating potential N-linked glycosylation of MdPGIP1. The molecular mass of non-glycosylated MdPGIP1 was calculated as 36.615 kDa and the theoretical isoelectric point as 6.98. Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs).

Towards fast, rigorous and efficient conformational sampling of biomolecules: Advances in accelerated molecular dynamics.

PubMed

Doshi, Urmi; Hamelberg, Donald

2015-05-01

Accelerated molecular dynamics (aMD) has been proven to be a powerful biasing method for enhanced sampling of biomolecular conformations on general-purpose computational platforms. Biologically important long timescale events that are beyond the reach of standard molecular dynamics can be accessed without losing the detailed atomistic description of the system in aMD. Over other biasing methods, aMD offers the advantages of tuning the level of acceleration to access the desired timescale without any advance knowledge of the reaction coordinate. Recent advances in the implementation of aMD and its applications to small peptides and biological macromolecules are reviewed here along with a brief account of all the aMD variants introduced in the last decade. In comparison to the original implementation of aMD, the recent variant in which all the rotatable dihedral angles are accelerated (RaMD) exhibits faster convergence rates and significant improvement in statistical accuracy of retrieved thermodynamic properties. RaMD in conjunction with accelerating diffusive degrees of freedom, i.e. dual boosting, has been rigorously tested for the most difficult conformational sampling problem, protein folding. It has been shown that RaMD with dual boosting is capable of efficiently sampling multiple folding and unfolding events in small fast folding proteins. RaMD with the dual boost approach opens exciting possibilities for sampling multiple timescales in biomolecules. While equilibrium properties can be recovered satisfactorily from aMD-based methods, directly obtaining dynamics and kinetic rates for larger systems presents a future challenge. This article is part of a Special Issue entitled Recent developments of molecular dynamics. Copyright © 2014 Elsevier B.V. All rights reserved.

Relationship between consecutive deterioration of mean deviation value and progression of visual field defect in open-angle glaucoma.

PubMed

Naito, Tomoko; Yoshikawa, Keiji; Mizoue, Shiro; Nanno, Mami; Kimura, Tairo; Suzumura, Hirotaka; Takeda, Ryuji; Shiraga, Fumio

2015-01-01

To analyze the relationship between consecutive deterioration of mean deviation (MD) value and glaucomatous visual field (VF) progression in open-angle glaucoma (OAG), including primary OAG and normal tension glaucoma. The subjects of the study were patients undergoing treatment for OAG who had performed VF tests at least 10 times with a Humphrey field analyzer (SITA standard, C30-2 program). The VF progression was defined by a significantly negative MD slope (MD slope worsening) at the final VF test during the follow-up period. The relationship between the MD slope worsening and the consecutive deterioration of MD value were retrospectively analyzed. A total of 165 eyes of 165 patients were included in the analysis. Significant progression of VF defects was observed in 72 eyes of 72 patients (43.6%), while no significant progression was evident in 93 eyes of 93 patients (56.4%). There was significant relationship between the frequency of consecutive deterioration of MD value and MD slope worsening (P<0.0001, Cochran-Armitage trend test). A significant association was observed for MD slope worsening in the eyes with three (odds ratio: 2.1, P=0.0224) and four (odds ratio: 3.6, P=0.0008) consecutive deterioration of MD value in multiple logistic regression analysis, but no significant association in the eyes with two consecutive deterioration (odds ratio: 1.1, P=0.8282). The eyes with VF progression had significantly lower intraocular pressure reduction rate (P<0.01). This retrospective study has shown that three or more consecutive deterioration of MD value might be a predictor to future significant MD slope worsening in OAG.

Past major depression and smoking cessation outcome: a systematic review and meta-analysis update

PubMed Central

Hitsman, Brian; Papandonatos, George D.; McChargue, Dennis E.; DeMott, Andrew; Herrera, María José; Spring, Bonnie; Borrelli, Belinda; Niaura, Raymond

2012-01-01

Aims To update our prior meta-analysis that showed past major depression (MD+) to be unrelated to smoking cessation outcome [Hitsman et al. J Consult Clin Psychol 2003; 71:657–63]. Methods Eligible trials included 14 from our original review and 28 identified through an updated systematic review (2000–2009). We coded for assessment of past MD, exclusion for recent MD episode (MDE; ≤6 months versus no exclusion), duration/modality of cognitive behavioral treatment (CBT; face-to-face versus self-help), and other factors. To minimize influence of experimental treatments that may selectively benefit MD+ smokers, we analyzed placebo/lowest intensity control arms only. Study-specific odds ratios (ORs) for the effect of past MD on short-term (≤3 months) and long-term (≥6 months) abstinence were estimated and combined using random effects. Two-way interaction models of past MD with study methodology and treatment factors were used to evaluate hypothesized moderators of the past MD-abstinence association. Results MD+ smokers had 17% lower odds of short-term abstinence (n=35, OR=0.83, 95% CI=0.72–0.95, p=0.009) and 19% lower odds of long-term abstinence (n=38, OR=0.81, 95% CI=0.67–0.97, p=0.023) than MD− smokers after excluding the sole study of varenicline because of its antidepressant properties. The association between past MD and abstinence was affected by methodological (recent MDE exclusion, type of MD assessment) and treatment (CBT modality) factors. Conclusions Past major depression has a modest adverse effect on abstinence during and after smoking cessation treatment. An increased focus on the identification of effective treatments or treatment adaptations that eliminate this disparity in smoking cessation for MD+ smokers is needed. PMID:23072580

Dietary Intervention Restored Menses in Female Athletes with Exercise-Associated Menstrual Dysfunction with Limited Impact on Bone and Muscle Health

PubMed Central

Cialdella-Kam, Lynn; Guebels, Charlotte P.; Maddalozzo, Gianni F.; Manore, Melinda M.

2014-01-01

Exercise-related menstrual dysfunction (ExMD) is associated with low energy availability (EA), decreased bone mineral density (BMD), and increased risk of musculoskeletal injury. We investigated whether a 6-month carbohydrate-protein (CHO-PRO) supplement (360 kcal/day, 54 g CHO/day, 20 g PRO/day) intervention would improve energy status and musculoskeletal health and restore menses in female athletes (n = 8) with ExMD. At pre/post-intervention, reproductive and thyroid hormones, bone health (BMD, bone mineral content, bone markers), muscle strength/power and protein metabolism markers, profile of mood state (POMS), and energy intake (EI)/energy expenditure (7 day food/activity records) were measured. Eumenorrheic athlete controls with normal menses (Eumen); n = 10) were measured at baseline. Multiple linear regressions were used to evaluate differences between groups and pre/post-intervention blocking on participants. Improvements in EI (+382 kcal/day; p = 0.12), EA (+417 kcal/day; p = 0.17) and energy balance (EB; +466 kcal/day; p = 0.14) were observed with the intervention but were not statistically significant. ExMD resumed menses (2.6 ± 2.2-months to first menses; 3.5 ± 1.9 cycles); one remaining anovulatory with menses. Female athletes with ExMD for >8 months took longer to resume menses/ovulation and had lower BMD (low spine (ExMD = 3; Eumen = 1); low hip (ExMD = 2)) than those with ExMD for <8 months; for 2 ExMD the intervention improved spinal BMD. POMS fatigue scores were 15% lower in ExMD vs. Eumen (p = 0.17); POMS depression scores improved by 8% in ExMD (p = 0.12). EI, EA, and EB were similar between groups, but the intervention (+360 kcal/day) improved energy status enough to reverse ExMD despite no statistically significant changes in EI. Similar baseline EA and EB between groups suggests that some ExMD athletes are more sensitive to EA and EB fluctuations. PMID:25090245

Dietary intervention restored menses in female athletes with exercise-associated menstrual dysfunction with limited impact on bone and muscle health.

PubMed

Cialdella-Kam, Lynn; Guebels, Charlotte P; Maddalozzo, Gianni F; Manore, Melinda M

2014-07-31

Exercise-related menstrual dysfunction (ExMD) is associated with low energy availability (EA), decreased bone mineral density (BMD), and increased risk of musculoskeletal injury. We investigated whether a 6-month carbohydrate-protein (CHO-PRO) supplement (360 kcal/day, 54 g CHO/day, 20 g PRO/day) intervention would improve energy status and musculoskeletal health and restore menses in female athletes (n = 8) with ExMD. At pre/post-intervention, reproductive and thyroid hormones, bone health (BMD, bone mineral content, bone markers), muscle strength/power and protein metabolism markers, profile of mood state (POMS), and energy intake (EI)/energy expenditure (7 day food/activity records) were measured. Eumenorrheic athlete controls with normal menses (Eumen); n = 10) were measured at baseline. Multiple linear regressions were used to evaluate differences between groups and pre/post-intervention blocking on participants. Improvements in EI (+382 kcal/day; p = 0.12), EA (+417 kcal/day; p = 0.17) and energy balance (EB; +466 kcal/day; p = 0.14) were observed with the intervention but were not statistically significant. ExMD resumed menses (2.6 ± 2.2-months to first menses; 3.5 ± 1.9 cycles); one remaining anovulatory with menses. Female athletes with ExMD for >8 months took longer to resume menses/ovulation and had lower BMD (low spine (ExMD = 3; Eumen = 1); low hip (ExMD = 2)) than those with ExMD for <8 months; for 2 ExMD the intervention improved spinal BMD. POMS fatigue scores were 15% lower in ExMD vs. Eumen (p = 0.17); POMS depression scores improved by 8% in ExMD (p = 0.12). EI, EA, and EB were similar between groups, but the intervention (+360 kcal/day) improved energy status enough to reverse ExMD despite no statistically significant changes in EI. Similar baseline EA and EB between groups suggests that some ExMD athletes are more sensitive to EA and EB fluctuations.

A novel gene, MdSSK1, as a component of the SCF complex rather than MdSBP1 can mediate the ubiquitination of S-RNase in apple.

PubMed

Yuan, Hui; Meng, Dong; Gu, Zhaoyu; Li, Wei; Wang, Aide; Yang, Qing; Zhu, Yuandi; Li, Tianzhong

2014-07-01

As a core factor in S-RNase-based gametophytic self-incompatibility (GSI), the SCF (SKP1-Cullin1-F-box-Rbx1) complex (including pollen determinant SLF, S-locus-F-box) functions as an E3 ubiquitin ligase on non-self S-RNase. The SCF complex is formed by SKP1 bridging between SLF, CUL1, and Rbx1; however, it is not known whether an SCF complex lacking SKP1 can mediate the ubiquitination of S-RNase. Three SKP1-like genes from pollen were cloned based on the structural features of the SLF-interacting-SKP1-like (SSK) gene and the 'Golden Delicious' apple genome. These genes have a motif of five amino acids following the standard 'WAFE' at the C terminal and, in addition, contain eight sheets and two helices. All three genes were expressed exclusively in pollen. In the yeast two-hybrid and pull-down assays only one was found to interact with MdSFBB and MdCUL1, suggesting it is the SLF-interacting SKP1-like gene in apple which was named MdSSK1. In vitro experiments using MdSSK1, S2-MdSFBB1 (S2-Malus domestica S-locus-F-box brother) and MdCUL1 proteins incubated with S 2-RNase and ubiquitin revealed that the SCF complex ubiquitinylates S-RNase in vitro, while MdSBP1 (Malus domestica S-RNase binding protein 1) could not functionally replace MdSSK1 in the SCF complex in ubiquitinylating S-RNase. According to the above experiments, MdSBP1 is probably the only factor responsible for recognition with S-RNase, while not a component of the SCF complex, and an SCF complex containing MdSSK1 is required for mediating the ubiquitination of S-RNase. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Partially Glycosylated Dendrimers Block MD-2 and Prevent TLR4-MD-2-LPS Complex Mediated Cytokine Responses

PubMed Central

Barata, Teresa S.; Teo, Ian; Brocchini, Steve; Zloh, Mire; Shaunak, Sunil

2011-01-01

The crystal structure of the TLR4-MD-2-LPS complex responsible for triggering powerful pro-inflammatory cytokine responses has recently become available. Central to cell surface complex formation is binding of lipopolysaccharide (LPS) to soluble MD-2. We have previously shown, in biologically based experiments, that a generation 3.5 PAMAM dendrimer with 64 peripheral carboxylic acid groups acts as an antagonist of pro-inflammatory cytokine production after surface modification with 8 glucosamine molecules. We have also shown using molecular modelling approaches that this partially glycosylated dendrimer has the flexibility, cluster density, surface electrostatic charge, and hydrophilicity to make it a therapeutically useful antagonist of complex formation. These studies enabled the computational study of the interactions of the unmodified dendrimer, glucosamine, and of the partially glycosylated dendrimer with TLR4 and MD-2 using molecular docking and molecular dynamics techniques. They demonstrate that dendrimer glucosamine forms co-operative electrostatic interactions with residues lining the entrance to MD-2's hydrophobic pocket. Crucially, dendrimer glucosamine interferes with the electrostatic binding of: (i) the 4′phosphate on the di-glucosamine of LPS to Ser118 on MD-2; (ii) LPS to Lys91 on MD-2; (iii) the subsequent binding of TLR4 to Tyr102 on MD-2. This is followed by additional co-operative interactions between several of the dendrimer glucosamine's carboxylic acid branches and MD-2. Collectively, these interactions block the entry of the lipid chains of LPS into MD-2's hydrophobic pocket, and also prevent TLR4-MD-2-LPS complex formation. Our studies have therefore defined the first nonlipid-based synthetic MD-2 antagonist using both animal model-based studies of pro-inflammatory cytokine responses and molecular modelling studies of a whole dendrimer with its target protein. Using this approach, it should now be possible to computationally design additional macromolecular dendrimer based antagonists for other Toll Like Receptors. They could be useful for treating a spectrum of infectious, inflammatory and malignant diseases. PMID:21738462

MdPIN1b encodes a putative auxin efflux carrier and has different expression patterns in BC and M9 apple rootstocks.

PubMed

Gan, Zengyu; Wang, Yi; Wu, Ting; Xu, Xuefeng; Zhang, Xinzhong; Han, Zhenhai

2018-03-01

Lower promoter activity is closely associated with lower MdPIN1b expression in the M9 interstem, which might contribute to the dwarfing effect in apple trees. Apple trees grafted onto dwarfing rootstock Malling 9 (M9) produce dwarfing tree architecture with high yield and widely applying in production. Previously, we have reported that in Malus 'Red Fuji' (RF) trees growing on M9 interstem and Baleng Crab (BC) rootstock, IAA content was relatively higher in bark tissue of M9 interstem than that in scion or rootstock. As IAA polar transportation largely depends on the PIN-FORMED (PIN) auxin efflux carrier. Herein, we identify two putative auxin efflux carrier genes in Malus genus, MdPIN1a and MdPIN1b, which were closely related to the AtPIN1. We found that MdPIN1b was expressed preferentially in BC and M9, and the expression of MdPIN1b was significantly lower in the phloem of M9 interstem than that in the scion and rootstock. The distinct expression of MdPIN1b and IAA content were concentrated in the cambium and adjacent xylem or phloem, and MdPIN1b protein was localized on cell plasma membrane in onion epidermal cells transiently expressing 35S:MdPIN1b-GFP fusion protein. Interestingly, an MdPIN1b mutant allele in the promoter region upstream of M9 exhibited decreased MdPIN1b expression compared to BC. MdPIN1b over-expressing interstem in tobacco exhibited increased polar auxin transport. It is proposed that natural allelic differences decreased promoter activity is closely associated with lower MdPIN1b expression in the M9 interstem, which might limit the basipetal transport of auxin, and in turn might contribute to the dwarfing effect. Taken together, these results reveal allelic variation underlying an important apple rootstock trait, and specifically a novel molecular genetic mechanism underlying dwarfing mechanism.

A ‘modified de Gramont’ regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer

PubMed Central

Cheeseman, S L; Joel, S P; Chester, J D; Wilson, G; Dent, J T; Richards, F J; Seymour, M T

2002-01-01

The standard de Gramont (dG) regimen of fortnightly leucovorin, bolus fluorouracil and 22-h infusion of fluorouracil, d1+2, and the same regimen plus oxaliplatin, are effective but also cumbersome. We therefore present simplified ‘Modified de Gramont’ (MdG) regimens. Forty-six advanced gastrointestinal cancer patients entered a dose-exploring study of MdG, including an expanded cohort of colorectal cancer patients at optimum dose. Treatment (fortnightly) comprised: 2-h i.v.i. leucovorin (350 mg d,l-LV or 175 mg l-LV, not adjusted for patient surface area); bolus fluorouracil (400 mg m−2), then ambulatory 46-h fluorouracil infusion (2000–3600 mg m−2, cohort escalation). Subsequently, 62 colorectal patients (25 unpretreated; 37 fluorouracil-resistant) received MdG plus oxaliplatin (OxMdG) 85 mg m−2. Fluorouracil pharmacokinetics during MdG were compared with dG. The optimum fluorouracil doses for MdG alone were determined as 400 mg m−2 bolus + 2800 mg m−2 46-h infusion. A lower dose of 400 mg m−2 bolus + 2400 mg m−2 infusion which, like dG produces minimal toxicity, was chosen for the OxMdG combination. Fluorouracil exposure (AUC0–48 h) at this lower dose is equivalent to dG. With OxMdG, grade 3–4 toxicity was rare (neutropenia 2.8% cycles; vomiting or diarrhoea <1% cycles), but despite this there were two infection-associated deaths. Oxaliplatin was omitted for cumulative neurotoxicity in 17 out of 62 patients. Objective responses in colorectal cancer patients were: 1st-line MdG (22 assessable): PR=36%, NC=32%, PD=32%. 1st-line OxMdG (24 assessable): CR/PR=72%; NC=20%; PD=8%; 2nd line OxMdG (34 assessable): PR=12%; NC=38%; PD=50%. MdG and OxMdG are convenient and well-tolerated. OxMdG was particularly active as 1st-line treatment of advanced colorectal cancer. Both regimens are being further evaluated in the current UK MRC phase III trial. British Journal of Cancer (2002) 87, 393–399. doi:10.1038/sj.bjc.6600467 www.bjcancer.com © 2002 Cancer Research UK PMID:12177775

77 FR 16929 - Safety Zones; Fireworks Displays within the Fifth Coast Guard District

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-23

...; Chesapeake Bay, Chesapeake Beach, MD; Potomac River, Charles County, MD; Potomac River, Charles County, MD...'' N, longitude 076[deg]26'07.6'' W and Patuxent River, Solomons Island, MD, centered at approximate position latitude 38[deg]19'21'' N, longitude 076[deg]27'55'' W. All coordinates for these safety zones...

76 FR 71369 - Robert G. Crummie, M.D.; Decision and Order

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-17

... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 10-60] Robert G. Crummie, M.D... Registration, BC2964965, issued to Robert G. Crummie, M.D., be, and it hereby is, revoked. I further order that any pending application of Robert G. Crummie, M.D., to renew or modify his registration, be, and it...

78 FR 19012 - Pawan Kumar Jain, M.D.; Decision And Order

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-28

... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 13-13] Pawan Kumar Jain, M.D...), I order that DEA Certificate of Registration BJ5128067, issued to Pawan Kumar Jain, M.D., be, and it hereby is, revoked. I further order that any pending application of Pawan Kumar Jain, M.D., to renew or...

Directory of Organizational Technical Report Acronym Codes (DOTRAC)

DTIC Science & Technology

1994-07-01

TM - Technical memo report........................................................... TMR- Technical news bulletin...BETHESDA 418182 MD DTRC- TM -12 DAVID TAYLOR RESEARCH CENTER BETHESDA 418631 MD SHIP SYSTEMS INTEGRATION DEPT DTRC- TM -14 DAVID TAYLOR RESEARCH CENTER...BETHESDA 419277 MD SHIP ELECTROMAGNETIC SIGNATURES DEPT DTRC- TM -15 DAVID TAYLOR RESEARCH CENTER BETHESDA 418173 MD SHIP HYDROMECHANICS DEPT DTRC- TM -16 DAVID

Applicability of effective fragment potential version 2 - Molecular dynamics (EFP2-MD) simulations for predicting excess properties of mixed solvents

NASA Astrophysics Data System (ADS)

Kuroki, Nahoko; Mori, Hirotoshi

2018-02-01

Effective fragment potential version 2 - molecular dynamics (EFP2-MD) simulations, where the EFP2 is a polarizable force field based on ab initio electronic structure calculations were applied to water-methanol binary mixture. Comparing EFP2s defined with (aug-)cc-pVXZ (X = D,T) basis sets, it was found that large sets are necessary to generate sufficiently accurate EFP2 for predicting mixture properties. It was shown that EFP2-MD could predict the excess molar volume. Since the computational cost of EFP2-MD are far less than ab initio MD, the results presented herein demonstrate that EFP2-MD is promising for predicting physicochemical properties of novel mixed solvents.

Auditory selective attention in adolescents with major depression: An event-related potential study.

PubMed

Greimel, E; Trinkl, M; Bartling, J; Bakos, S; Grossheinrich, N; Schulte-Körne, G

2015-02-01

Major depression (MD) is associated with deficits in selective attention. Previous studies in adults with MD using event-related potentials (ERPs) reported abnormalities in the neurophysiological correlates of auditory selective attention. However, it is yet unclear whether these findings can be generalized to MD in adolescence. Thus, the aim of the present ERP study was to explore the neural mechanisms of auditory selective attention in adolescents with MD. 24 male and female unmedicated adolescents with MD and 21 control subjects were included in the study. ERPs were collected during an auditory oddball paradigm. Depressive adolescents tended to show a longer N100 latency to target and non-target tones. Moreover, MD subjects showed a prolonged latency of the P200 component to targets. Across groups, longer P200 latency was associated with a decreased tendency of disinhibited behavior as assessed by a behavioral questionnaire. To be able to draw more precise conclusions about differences between the neural bases of selective attention in adolescents vs. adults with MD, future studies should include both age groups and apply the same experimental setting across all subjects. The study provides strong support for abnormalities in the neurophysiolgical bases of selective attention in adolecents with MD at early stages of auditory information processing. Absent group differences in later ERP components reflecting voluntary attentional processes stand in contrast to results reported in adults with MD and may suggest that adolescents with MD possess mechanisms to compensate for abnormalities in the early stages of selective attention. Copyright © 2014 Elsevier B.V. All rights reserved.

Behavior of visual field index in advanced glaucoma.

PubMed

Rao, Harsha L; Senthil, Sirisha; Choudhari, Nikhil S; Mandal, Anil K; Garudadri, Chandra S

2013-01-14

To evaluate the magnitude of Visual Field Index (VFI) change attributable to change in the estimation algorithm from the pattern deviation probability plot (PDPP) to the total deviation probability plot (TDPP) when the mean deviation (MD) crosses -20 decibels (dB). In a retrospective study, 37 stable glaucoma eyes in which MD of the VFs crossed -20 dB were identified. For each eye, a pair of VFs was selected so that one VF of the pair had a MD better than but close to -20 dB and the other had a MD worse than but again close to -20 dB. The change in VFI in the VF pairs and its associations with the number of points in probability plots with normal threshold sensitivities were evaluated. Similar pairs of VFs from 28 stable glaucoma eyes where the MD crossed -10 dB were chosen as controls. The change in VFI in VF pairs when the MD crossed 20 dB ranged from 3% to 33% (median: 15%), while the change when MD crossed -10 dB ranged from 1% to 8% (median: 4%). Difference in the number of points with normal threshold sensitivities in PDPP when MD was better than -20 dB compared to those in TDPP when MD crossed -20 dB significantly influenced the VFI change (R(2) = 0.65). Considering the eccentricity of these points further explained the VFI change (R(2) = 0.81). The decrease in VFI when MD crosses -20 dB can be highly variable. This has to be considered with the use of VFI in clinical and research settings.

Clinical Value of Vestibular Evoked Myogenic Potential in Assessing the Stage and Predicting the Hearing Results in Ménière's Disease.

PubMed

Kim, Min-Beom; Choi, Jeesun; Park, Ga Young; Cho, Yang-Sun; Hong, Sung Hwa; Chung, Won-Ho

2013-06-01

Our goal was to find the clinical value of cervical vestibular evoked myogenic potential (VEMP) in Ménière's disease (MD) and to evaluate whether the VEMP results can be useful in assessing the stage of MD. Furthermore, we tried to evaluate the clinical effectiveness of VEMP in predicting hearing outcomes. The amplitude, peak latency and interaural amplitude difference (IAD) ratio were obtained using cervical VEMP. The VEMP results of MD were compared with those of normal subjects, and the MD stages were compared with the IAD ratio. Finally, the hearing changes were analyzed according to their VEMP results. In clinically definite unilateral MD (n=41), the prevalence of cervical VEMP abnormality in the IAD ratio was 34.1%. When compared with normal subjects (n=33), the VEMP profile of MD patients showed a low amplitude and a similar latency. The mean IAD ratio in MD was 23%, which was significantly different from that of normal subjects (P=0.01). As the stage increased, the IAD ratio significantly increased (P=0.09). After stratification by initial hearing level, stage I and II subjects (hearing threshold, 0-40 dB) with an abnormal IAD ratio showed a decrease in hearing over time compared to those with a normal IAD ratio (P=0.08). VEMP parameters have an important clinical role in MD. Especially, the IAD ratio can be used to assess the stage of MD. An abnormal IAD ratio may be used as a predictor of poor hearing outcomes in subjects with early stage MD.

Mediodorsal thalamus hypofunction impairs flexible goal-directed behavior.

PubMed

Parnaudeau, Sébastien; Taylor, Kathleen; Bolkan, Scott S; Ward, Ryan D; Balsam, Peter D; Kellendonk, Christoph

2015-03-01

Cognitive inflexibility is a core symptom of several mental disorders including schizophrenia. Brain imaging studies in schizophrenia patients performing cognitive tasks have reported decreased activation of the mediodorsal thalamus (MD). Using a pharmacogenetic approach to model MD hypofunction, we recently showed that decreasing MD activity impairs reversal learning in mice. While this demonstrates causality between MD hypofunction and cognitive inflexibility, questions remain about the elementary cognitive processes that account for the deficit. Using the Designer Receptors Exclusively Activated by Designer Drugs system, we reversibly decreased MD activity during behavioral tasks assessing elementary cognitive processes inherent to flexible goal-directed behaviors, including extinction, contingency degradation, outcome devaluation, and Pavlovian-to-instrumental transfer (n = 134 mice). While MD hypofunction impaired reversal learning, it did not affect the ability to learn about nonrewarded cues or the ability to modulate action selection based on the outcome value. In contrast, decreasing MD activity delayed the ability to adapt to changes in the contingency between actions and their outcomes. In addition, while Pavlovian learning was not affected by MD hypofunction, decreasing MD activity during Pavlovian learning impaired the ability of conditioned stimuli to modulate instrumental behavior. Mediodorsal thalamus hypofunction causes cognitive inflexibility reflected by an impaired ability to adapt actions when their consequences change. Furthermore, it alters the encoding of environmental stimuli so that they cannot be properly utilized to guide behavior. Modulating MD activity could be a potential therapeutic strategy for promoting adaptive behavior in human subjects with cognitive inflexibility. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Comparative levels of excessive daytime sleepiness in common medical disorders.

PubMed

Stroe, Alice F; Roth, Thomas; Jefferson, Catherine; Hudgel, David W; Roehrs, Timothy; Moss, Kenneth; Drake, Christopher L

2010-10-01

Sleep restriction and sleep disorders are common causes of excessive daytime sleepiness (EDS). Medical disorders (MD) can also cause EDS, but previous studies have used non-standardized measures, selected samples, or have examined EDS in singular disorders. This study describes the relative degree of EDS associated with medical disorders to provide comparative data across a range of common medical conditions in a large unselected community-based sample. Responses of 2612 individuals (aged 18-65) were assessed after excluding those with suspected sleep disordered breathing, narcolepsy, and shift workers. Participants across a range of medical disorders were evaluated using the Epworth Sleepiness Scale (ESS) and patient reports of nocturnal sleep. Sixty-seven percent of the sample reported a MD. The prevalence of EDS (ESS>or=10) was 31.4% in individuals with MD and increased as a function of a number of MD (0 MD=29.4%, 1 MD=28.4%, 2 MD=31.0%, 3 MD=35.3%, 4 MD=38.4%). Disorders which were independent predictors of EDS were ulcers OR=2.21 (95% CI=1.35-3.61), migraines OR=1.36 (95% CI=1.08-1.72), and depression OR=1.46 (95% CI=1.16-1.83) after controlling for other conditions, age, gender, time in bed, caffeine, smoking and alcohol use. Participants with ulcers had the highest prevalence of sleepiness, 50.0%, as well as the highest level of problems falling asleep (40.8%) and awakenings during the night (62.5%). Individuals with ulcers, migraines, and depression have independent and clinically significant levels of EDS relative to other common MD.

Impacts of Mass-dimension and Area-dimension relationships on retrieval ice particle effective radius from radar and lidar measurements

NASA Astrophysics Data System (ADS)

Ham, S. H.; Kato, S.; Rose, F. G.

2016-12-01

In the retrieval of ice clouds from Radar and Lidar Measurements, mass-Dimension (m-D) and Area-Dimension (A-D) relationships are often used to describe nonspherical ice particle shapes. This study analytically investigates how the assumption of m-D and A-D relationships affects retrieval of ice effective radius. We use gamma and lognormal particle distributions and integrate optical parameters over the size distribution. The effective radius is expressed as a function of radar reflectivity factor, visible extinction coefficient, and parameters describing m-D and A-D relationships. The analytic expressions are used for converting effective radius retrieved from one set of m-D and A-D relationships into that with another set of m-D and A-D, including plates, solid columns, bullets, and mixture of different habits. The conversion method can be used for consistent radiative transfer simulation with cloud retrieval algorithms. In addition, when we want to merge cloud effective radii retrieved from different m-D and A-D, the conversion method can be efficiently used to remove undesired biases caused by m-D and A-D assumptions. Furthermore, the sensitivity of the effective radius to m-D and A-D relationships can be quantified by taking the first derivative of the effective radius with respect to parameters expressing the m-D and A-D relationships.

Functional identification and regulatory analysis of Δ6-fatty acid desaturase from the oleaginous fungus Mucor sp. EIM-10.

PubMed

Jiang, Xianzhang; Liu, Hongjiao; Niu, Yongchao; Qi, Feng; Zhang, Mingliang; Huang, Jianzhong

2017-03-01

To enlarge the diversity of the desaturases associated with PUFA biosynthesis and to better understand the transcriptional regulation of desaturases, a Δ 6 -desaturase gene (Md6) from Mucor sp. and its 5'-upstream sequence was functionally identified in Saccharomyces cerevisiae. Expression of the Δ 6 -fatty acid desaturase (Md6) in S. cerevisiae showed that Md6 could convert linolenic acid to γ-linolenic acid. Computational analysis of the promoter of Md6 suggested it contains several eukaryotic fundamental transcription regulatory elements. In vivo functional analysis of the promoter showed the 5'-upstream sequence of Md6 could initiate expression of GFP and Md6 itself in S. cerevisiae. A series deletion analysis of the promoter suggested that sequence between -919 to -784 bp (relative to start site) named as eMd6 is the key factor for high activity of Δ 6 -desaturase. The activity of Δ 6 -desaturase was increased by 2.8-fold and 2.5-fold when the eMd6 sequence was placed upstream of -434 with forward or reverse orientations respectively. To our best knowledge, the native promoter of Md6 from Mucor is the strongest promoter for Δ 6 -desaturase reported so far and the sequence between -919 to -784 bp is an enhancer for Δ 6 -desaturase activity.

Trypsin-sensitive modulation of intestinal epithelial MD-2 as mechanism of lipopolysaccharide tolerance.

PubMed

Cario, Elke; Golenbock, Douglas T; Visintin, Alberto; Rünzi, Michael; Gerken, Guido; Podolsky, Daniel K

2006-04-01

Intestinal epithelial cells (IEC) are constantly exposed to both high concentrations of the bacterial ligand LPS and the serine protease trypsin. MD-2, which contains multiple trypsin cleavage sites, is an essential accessory glycoprotein required for LPS recognition and signaling through TLR4. The aim of this study was to characterize the expression and subcellular distribution of intestinal epithelial MD-2 and to delineate potential functional interactions with trypsin and then alteration in inflammatory bowel disease (IBD). Although MD-2 protein expression was minimal in primary IEC of normal colonic or ileal mucosa, expression was significantly increased in IEC from patients with active IBD colitis, but not in ileal areas from patients with severe Crohn's disease. Endogenous MD-2 was predominantly retained in the calnexin-calreticulin cycle of the endoplasmic reticulum; only a small fraction was exported to the Golgi. MD-2 expression correlated inversely with trypsin activity. Biochemical evidence and in vitro experiments demonstrated that trypsin exposure resulted in extensive proteolysis of endogenous and soluble MD-2 protein, but not of TLR4 in IEC, and was associated with desensitization of IEC to LPS. In conclusion, the present study suggests that endoplasmic reticulum-associated MD-2 expression in IBD may be altered by ileal protease in inflammation, leading to impaired LPS recognition and hyporesponsiveness through MD-2 proteolysis in IEC, thus implying a physiologic mechanism that helps maintain LPS tolerance in the intestine.

Hard- and soft-tissue profiles of the midface region in patients with skeletal Class III malocclusion using cone-beam computed tomography multiplanar-reconstructed image analysis.

PubMed

Kim, Bomi; Lee, Hyung-Chul; Kim, Seong-Hun; Kim, Yongil; Son, Woosung; Kim, Seong Sik

2018-05-01

This study examined cone-beam computed tomography (CBCT)-derived multiplanar-reconstructed (MPR) cross-sections to clarify the salient characteristics of patients with skeletal class III malocclusion with midface deficiency (MD). The horizontal and sagittal plane intersection points were identified for middle-third facial analysis in 40 patients in the MD or normal (N) groups. MPR images acquired parallel to each horizontal plane were used for length and angular measurements. A comparison of the MD and N groups revealed significant differences in the zygoma prominence among female patients. The convex zygomatic area in the N group was larger than that in the MD group, and the inferior part of the midface in the N group was smaller than that in the MD group for both male and female patients. A significant difference was observed in the concave middle maxillary area among male patients. This study was conducted to demonstrate the difference between MD and normal face through MPR images derived from CBCT. Male patients in the MD group had a more flattened face than did those in the N group. Female patients in the MD group showed a concave-shaped lower section of the zygoma, which tended to have more severe MD. These findings indicate that orthognathic surgery to improve skeletal discrepancy requires different approaches in male and female patients.

Retrospective review of adverse incidents involving passengers seated in wheeled mobility devices while traveling in large accessible transit vehicles.

PubMed

Frost, Karen L; Bertocci, Gina

2010-04-01

Characterize wheeled mobility device (WhMD) adverse incidents on large accessible transit vehicles (LATVs) based on vehicle motion, WhMD activity during incident, incident scenario and injury. Retrospective records review. WhMD passengers traveling on LATVs while remaining seated in their. Adverse incidents characterized based on vehicle motion, WhMD activity during incident, and incident scenario. Injury characterized based on outcome, medical attention sought, vehicle activity, WhMD activity and incident scenario. 115 WhMD-related incident reports for years 2000-2005 were analyzed. Most incidents occurred when the LATV was stopped (73.9%), during ingress/egress (42.6%), and at the securement station (33.9%) when the LATV was moving. The combination of WhMD tipping and passenger falling (43.4%) occurred most frequently, and was 1.8 times more likely to occur during ingress/egress than at the securement station. One-third (33.6%) of all incidents resulted in injury, and injuries were equally distributed between ingress/egress (43.6%) and at the securement station (43.6%). WhMD users have a greater chance of incurring injury during ingress/egress than during transit. Research is needed to objectively assess real world transportation experiences of WhMD passengers, and to assess the adequacy of existing federal legislation/guidelines for accessible ramps used in public transportation. Copyright 2009 IPEM. Published by Elsevier Ltd. All rights reserved.

The influence of estradiol on muscle damage and leg strength after intense eccentric exercise.

PubMed

Minahan, Clare; Joyce, Sarah; Bulmer, Andrew C; Cronin, Neil; Sabapathy, Surendran

2015-07-01

To examine the influence of estradiol on muscle damage and leg strength after intense eccentric exercise. Eight men (MEN), eight normally menstruating women (WomenNM), and eight women using oral contraceptives (WomenOC) participated in this study. Subjects performed 240 maximal-effort bilateral eccentric contractions of the quadriceps muscle groups designed to elicit exercise-induced muscle damage (EiMD). Serum creatine kinase (CK), myoglobin (Mb), and fatty acid-binding protein (FABP) concentrations were measured before (pre-) EiMD, as well as 0, 6, 24, and 48 h post-EiMD. Peak isometric quadriceps torque (i.e., leg strength) was measured pre-EiMD, as well as 24 and 48 h post-EiMD. The increases in CK, Mb, and FABP concentrations from pre- to post-EiMD were greater in MEN (10-fold, 15-fold, and fourfold, respectively) and WomenOC (sevenfold, 11-fold, and ninefold) compared with WomenNM (five-, six-, and threefold; p < 0.05). The decline in leg strength was about 10 % pre- to 24 h post-EiMD in all groups and decreased a further 10-15 % by 48 h post-EiMD in the MEN and WomenOC only. Our findings suggest an important role of estradiol in blunting the muscle damage response to intense eccentric exercise and preserving muscle function after EiMD.

Identification of Rare Lewis Oligosaccharide Conformers in Aqueous Solution Using Enhanced Sampling Molecular Dynamics.

PubMed

Alibay, Irfan; Burusco, Kepa K; Bruce, Neil J; Bryce, Richard A

2018-03-08

Determining the conformations accessible to carbohydrate ligands in aqueous solution is important for understanding their biological action. In this work, we evaluate the conformational free-energy surfaces of Lewis oligosaccharides in explicit aqueous solvent using a multidimensional variant of the swarm-enhanced sampling molecular dynamics (msesMD) method; we compare with multi-microsecond unbiased MD simulations, umbrella sampling, and accelerated MD approaches. For the sialyl Lewis A tetrasaccharide, msesMD simulations in aqueous solution predict conformer landscapes in general agreement with the other biased methods and with triplicate unbiased 10 μs trajectories; these simulations find a predominance of closed conformer and a range of low-occupancy open forms. The msesMD simulations also suggest closed-to-open transitions in the tetrasaccharide are facilitated by changes in ring puckering of its GlcNAc residue away from the 4 C 1 form, in line with previous work. For sialyl Lewis X tetrasaccharide, msesMD simulations predict a minor population of an open form in solution corresponding to a rare lectin-bound pose observed crystallographically. Overall, from comparison with biased MD calculations, we find that triplicate 10 μs unbiased MD simulations may not be enough to fully sample glycan conformations in aqueous solution. However, the computational efficiency and intuitive approach of the msesMD method suggest potential for its application in glycomics as a tool for analysis of oligosaccharide conformation.

Preparing MD-PhD students for clinical rotations: navigating the interface between PhD and MD training.

PubMed

Goldberg, Charles; Insel, Paul A

2013-06-01

Many aspects of MD-PhD training are not optimally designed to prepare students for their future roles as translational clinician-scientists. The transition between PhD research efforts and clinical rotations is one hurdle that must be overcome. MD-PhD students have deficits in clinical skills compared with those of their MD-only colleagues at the time of this transition. Reimmersion programs (RPs) targeted to MD-PhD students have the potential to help them navigate this transition.The authors draw on their experience creating and implementing an RP that incorporates multiple types of activities (clinical exam review, objective structured clinical examination, and supervised practice in patient care settings) designed to enhance the participants' skills and readiness for clinical efforts. On the basis of this experience, they note that MD-PhD students' time away from the clinical environment negatively affects their clinical skills, causing them to feel underprepared for clinical rotations. The authors argue that participation in an RP can help students feel more comfortable speaking with and examining patients and decrease their anxiety regarding clinical encounters. The authors propose that RPs can have positive outcomes for improving the transition from PhD to clinical MD training in dual-degree programs. Identifying and addressing this and other transitions need to be considered to improve the educational experience of MD-PhD students.

An apple CIPK protein kinase targets a novel residue of AREB transcription factor for ABA-dependent phosphorylation.

PubMed

Ma, Qi-Jun; Sun, Mei-Hong; Lu, Jing; Liu, Ya-Jing; You, Chun-Xiang; Hao, Yu-Jin

2017-10-01

Phytohormone abscisic acid (ABA) regulates many important processes in plants. It is a major molecule facilitating signal transduction during the abiotic stress response. In this study, an ABA-inducible transcription factor gene, MdAREB2, was identified in apple. Transgenic analysis was performed to characterize its function in ABA sensitivity. Overexpression of the MdAREB2 gene increased ABA sensitivity in the transgenic apple compared with the wild-type (WT) control. In addition, it was found that the protein MdAREB2 was phosphorylated at a novel site Thr 411 in response to ABA. A yeast two-hybridization screen of an apple cDNA library demonstrated that a protein kinase, MdCIPK22, interacted with MdAREB2. Their interaction was further verified with Pull Down and Co-IP assays. A series of transgenic analyses in apple calli and plantlets showed that MdCIPK22 was required for ABA-induced phosphorylation at Thr 411 of the MdAREB2 protein and enhanced its stability and transcriptional activity. Finally, it was found that MdCIPK22 increased ABA sensitivity in an MdAREB2-dependent manner. Our findings indicate a novel phosphorylation site in CIPK-AREB regulatory module for the ABA signalling pathway, which would be helpful for researchers to identify the functions of uncharacterized homologs in the future. © 2017 John Wiley & Sons Ltd.

Visual experience and subsequent sleep induce sequential plastic changes in putative inhibitory and excitatory cortical neurons

PubMed Central

Aton, Sara J.; Broussard, Christopher; Dumoulin, Michelle; Seibt, Julie; Watson, Adam; Coleman, Tammi; Frank, Marcos G.

2013-01-01

Ocular dominance plasticity in the developing primary visual cortex is initiated by monocular deprivation (MD) and consolidated during subsequent sleep. To clarify how visual experience and sleep affect neuronal activity and plasticity, we continuously recorded extragranular visual cortex fast-spiking (FS) interneurons and putative principal (i.e., excitatory) neurons in freely behaving cats across periods of waking MD and post-MD sleep. Consistent with previous reports in mice, MD induces two related changes in FS interneurons: a response shift in favor of the closed eye and depression of firing. Spike-timing–dependent depression of open-eye–biased principal neuron inputs to FS interneurons may mediate these effects. During post-MD nonrapid eye movement sleep, principal neuron firing increases and becomes more phase-locked to slow wave and spindle oscillations. Ocular dominance (OD) shifts in favor of open-eye stimulation—evident only after post-MD sleep—are proportional to MD-induced changes in FS interneuron activity and to subsequent sleep-associated changes in principal neuron activity. OD shifts are greatest in principal neurons that fire 40–300 ms after neighboring FS interneurons during post-MD slow waves. Based on these data, we propose that MD-induced changes in FS interneurons play an instructive role in ocular dominance plasticity, causing disinhibition among open-eye–biased principal neurons, which drive plasticity throughout the visual cortex during subsequent sleep. PMID:23300282

Validity of the Medical College Admission Test for Predicting MD-PhD Student Outcomes

ERIC Educational Resources Information Center

Bills, James L.; VanHouten, Jacob; Grundy, Michelle M.; Chalkley, Roger; Dermody, Terence S.

2016-01-01

The Medical College Admission Test (MCAT) is a quantitative metric used by MD and MD-PhD programs to evaluate applicants for admission. This study assessed the validity of the MCAT in predicting training performance measures and career outcomes for MD-PhD students at a single institution. The study population consisted of 153 graduates of the…

Evaluation of Factors Affecting Vaccine Efficacy of Recombinant Marek's Disease Virus Lacking the Meq Oncogene in Chickens

USDA-ARS?s Scientific Manuscript database

We have previously reported that deletion of Meq gene from oncogenic rMd5 virus rendered it apathogenic for chickens. Here we examined multiple factors affecting Marek’s disease (MD) vaccine efficacy of this non-pathogenic recombinant Meq null rMd5 virus (rMd5deltaMeq). These factors included host g...

Accelerated molecular dynamics simulations of protein folding.

PubMed

Miao, Yinglong; Feixas, Ferran; Eun, Changsun; McCammon, J Andrew

2015-07-30

Folding of four fast-folding proteins, including chignolin, Trp-cage, villin headpiece and WW domain, was simulated via accelerated molecular dynamics (aMD). In comparison with hundred-of-microsecond timescale conventional molecular dynamics (cMD) simulations performed on the Anton supercomputer, aMD captured complete folding of the four proteins in significantly shorter simulation time. The folded protein conformations were found within 0.2-2.1 Å of the native NMR or X-ray crystal structures. Free energy profiles calculated through improved reweighting of the aMD simulations using cumulant expansion to the second-order are in good agreement with those obtained from cMD simulations. This allows us to identify distinct conformational states (e.g., unfolded and intermediate) other than the native structure and the protein folding energy barriers. Detailed analysis of protein secondary structures and local key residue interactions provided important insights into the protein folding pathways. Furthermore, the selections of force fields and aMD simulation parameters are discussed in detail. Our work shows usefulness and accuracy of aMD in studying protein folding, providing basic references in using aMD in future protein-folding studies. © 2015 Wiley Periodicals, Inc.

Transcription Factor AREB2 Is Involved in Soluble Sugar Accumulation by Activating Sugar Transporter and Amylase Genes.

PubMed

Ma, Qi-Jun; Sun, Mei-Hong; Lu, Jing; Liu, Ya-Jing; Hu, Da-Gang; Hao, Yu-Jin

2017-08-01

Sugars play important roles in plant growth and development, crop yield and quality, as well as responses to abiotic stresses. Abscisic acid (ABA) is a multifunctional hormone. However, the exact mechanism by which ABA regulates sugar accumulation is largely unknown in plants. Here, we tested the expression profile of several sugar transporter and amylase genes in response to ABA treatment. MdSUT2 and MdAREB2 were isolated and genetically transformed into apple ( Malus domestica ) to investigate their roles in ABA-induced sugar accumulation. The MdAREB2 transcription factor was found to bind to the promoters of the sugar transporter and amylase genes and activate their expression. Both MdAREB2 and MdSUT2 transgenic plants produced more soluble sugars than controls. Furthermore, MdAREB2 promoted the accumulation of sucrose and soluble sugars in an MdSUT2 -dependent manner. Our results demonstrate that the ABA-responsive transcription factor MdAREB2 directly activates the expression of amylase and sugar transporter genes to promote soluble sugar accumulation, suggesting a mechanism by which ABA regulates sugar accumulation in plants. © 2017 American Society of Plant Biologists. All Rights Reserved.

Understanding the link between feelings of mental defeat, self-efficacy and the experience of chronic pain.

PubMed

Hazeldine-Baker, Charlotte E; Salkovskis, Paul M; Osborn, Mike; Gauntlett-Gilbert, Jeremy

2018-05-01

'Mental defeat' (MD) has been identified among people with chronic pain as a type of self-processing related to social role and rank. Research has linked it to anxiety, pain interference and functional disability. The relationship between MD and other cognitive constructs, such as hopelessness and depression, remains poorly understood. This study considers the association between MD, pain symptomatology and self-efficacy in the context of other cognitive factors. In total, 59 participants completed a questionnaire pack assessing anxiety, depression, hopelessness, pain catastrophising and MD in order to examine the relationship with pain symptomatology and self-efficacy. Linear multiple regression analyses showed that anxiety was most strongly associated with pain symptomatology, accounting for 26% of the variance, while catastrophising showed the strongest association with sensory pain and MD the strongest association with affective pain. Finally, MD was found to be strongly associated with pain-related self-efficacy, accounting for 47% of the variance. This research has demonstrated the potential importance of assessing MD in chronic pain patients, suggesting that targeting these cognitions during interventions and therapy could be valuable. Furthermore, the study indicates that MD differs from related cognitive constructs involved in pain, such as depression, hopelessness and catastrophising.

Fractions Learning in Children With Mathematics Difficulties.

PubMed

Tian, Jing; Siegler, Robert S

Learning fractions is difficult for children in general and especially difficult for children with mathematics difficulties (MD). Recent research on developmental and individual differences in fraction knowledge of children with MD and typically achieving (TA) children has demonstrated that U.S. children with MD start middle school behind their TA peers in fraction understanding and fall further behind during middle school. In contrast, Chinese children, who like the MD children in the United States score in the bottom one third of the distribution in their country, possess reasonably good fraction understanding. We interpret these findings within the framework of the integrated theory of numerical development. By emphasizing the importance of fraction magnitude knowledge for numerical understanding in general, the theory proved useful for understanding differences in fraction knowledge between MD and TA children and for understanding how knowledge can be improved. Several interventions demonstrated the possibility of improving fraction magnitude knowledge and producing benefits that generalize to fraction arithmetic learning among children with MD. The reasonably good fraction understanding of Chinese children with MD and several successful interventions with U.S. students provide hope for the improvement of fraction knowledge among American children with MD.

Differentiating the levels of risk for muscle dysmorphia among Hungarian male weightlifters: a factor mixture modeling approach.

PubMed

Babusa, Bernadett; Czeglédi, Edit; Túry, Ferenc; Mayville, Stephen B; Urbán, Róbert

2015-01-01

Muscle dysmorphia (MD) is a body image disturbance characterized by a pathological preoccupation with muscularity. The study aimed to differentiate the levels of risk for MD among weightlifters and to define a tentative cut-off score for the Muscle Appearance Satisfaction Scale (MASS) for the identification of high risk MD cases. Hungarian male weightlifters (n=304) completed the MASS, the Exercise Addiction Inventory, and specific exercise and body image related questions. For the differentiation of MD, factor mixture modeling was performed, resulting in three independent groups: low-, moderate-, and high risk MD groups. The estimated prevalence of high risk MD in this sample of weightlifters was 15.1%. To determine a cut-off score for the MASS, sensitivity and specificity analyses were performed and a cut-off point of 63 was suggested. The proposed cut-off score for the MASS can be useful for the early detection of high risk MD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Correlates of muscle dysmorphia symptomatology in natural bodybuilders: Distinguishing factors in the pursuit of hyper-muscularity.

PubMed

Mitchell, Lachlan; Murray, Stuart B; Hoon, Matthew; Hackett, Daniel; Prvan, Tania; O'Connor, Helen

2017-09-01

Muscle dysmorphia (MD) is characterized by the pathological pursuit of muscularity and leanness, which includes eating- and exercise-related practices. The aim of this cross-sectional study was to identify correlations of MD symptomatology in natural bodybuilders. An online survey assessing diet, supplementation and training practices, and MD and eating disorder symptoms was completed by male bodybuilders with recent experience competing in a drug-tested competition. Sixty participants (age 29.6±7.1 years) completed the survey. Eating disorder scores (β=.298), rate of pre-competition weight loss (β=.307) and number of competitions (β=-.257) were significant predictors of MD. The association between the EAT-26 and MDDI underscores the salience of disordered eating pathology in presentations of MD. Supporting this, greater rate of pre-competition weight loss, which may reflect disordered eating practices, is also associated with MD symptomatology. The inverse association of competition experience suggests novice bodybuilders may display increased MD symptomatology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of Fact Retrieval Tutoring on Third-Grade Students with Math Difficulties with and without Reading Difficulties.

PubMed

Powell, Sarah R; Fuchs, Lynn S; Fuchs, Douglas; Cirino, Paul T; Fletcher, Jack M

2009-01-01

The purpose of this study was to assess the efficacy of fact retrieval tutoring as a function of math difficulty (MD) subtype, that is, whether students have MD alone (MD-only) or have concurrent difficulty with math and reading (MDRD). Third graders (n = 139) at two sites were randomly assigned, blocking by site and MD subtype, to four tutoring conditions: fact retrieval practice, conceptual fact retrieval instruction with practice, procedural computation/estimation instruction, and control (no tutoring). Tutoring occurred for 45 sessions over 15weeks for 15-25 minutes per session. Results provided evidence of an interaction between tutoring condition and MD subtype status for assessment of fact retrieval. For MD-only students, students in both fact retrieval conditions achieved comparably and outperformed MD-only students in the control group as well as those in the procedural computation/estimation instruction group. By contrast, for MDRD students, there were no significant differences among intervention conditions.

Effects of Fact Retrieval Tutoring on Third-Grade Students with Math Difficulties with and without Reading Difficulties

PubMed Central

Powell, Sarah R.; Fuchs, Lynn S.; Fuchs, Douglas; Cirino, Paul T.; Fletcher, Jack M.

2009-01-01

The purpose of this study was to assess the efficacy of fact retrieval tutoring as a function of math difficulty (MD) subtype, that is, whether students have MD alone (MD-only) or have concurrent difficulty with math and reading (MDRD). Third graders (n = 139) at two sites were randomly assigned, blocking by site and MD subtype, to four tutoring conditions: fact retrieval practice, conceptual fact retrieval instruction with practice, procedural computation/estimation instruction, and control (no tutoring). Tutoring occurred for 45 sessions over 15weeks for 15–25 minutes per session. Results provided evidence of an interaction between tutoring condition and MD subtype status for assessment of fact retrieval. For MD-only students, students in both fact retrieval conditions achieved comparably and outperformed MD-only students in the control group as well as those in the procedural computation/estimation instruction group. By contrast, for MDRD students, there were no significant differences among intervention conditions. PMID:19448840

Eating Disorders and Major Depression: Role of Anger and Personality

PubMed Central

Giovanni, Abbate-Daga; Carla, Gramaglia; Enrica, Marzola; Federico, Amianto; Maria, Zuccolin; Secondo, Fassino

2011-01-01

This study aimed to evaluate comorbidity for MD in a large ED sample and both personality and anger as clinical characteristics of patients with ED and MD. We assessed 838 ED patients with psychiatric evaluations and psychometric questionnaires: Temperament and Character Inventory, Eating Disorder Inventory-2, Beck Depression Inventory, and State-Trait Anger Expression Inventory. 19.5% of ED patients were found to suffer from comorbid MD and 48.7% reported clinically significant depressive symptomatology: patients with Anorexia Binge-Purging and Bulimia Nervosa were more likely to be diagnosed with MD. Irritable mood was found in the 73% of patients with MD. High Harm Avoidance (HA) and low Self-Directedness (SD) predicted MD independently of severity of the ED symptomatology, several clinical variables, and ED diagnosis. Assessing both personality and depressive symptoms could be useful to provide effective treatments. Longitudinal studies are needed to investigate the pathogenetic role of HA and SD for ED and MD. PMID:21977317

Five-year growth trajectories of kindergarten children with learning difficulties in mathematics.

PubMed

Morgan, Paul L; Farkas, George; Qiong Wu

2009-01-01

The investigators used data from the Early Childhood Longitudinal Study-Kindergarten Cohort (ECLS-K) to estimate whether and to what extent the timing and persistence of mathematics difficulties (MD) in kindergarten predicted children's first through fifth grade math growth trajectories. Results indicated that children persistently displaying MD (i.e., those experiencing MD in both fall and spring of kindergarten) had the lowest subsequent growth rates, children with MD in spring only had the second-lowest growth rates, and children with MD in the fall only (and who had thus recovered from their MD by the spring of kindergarten) had the next-lowest growth rates. The children who did not have MD in either fall or spring of kindergarten had the highest growth rates. These results were observed prior to and after statistical control for additional variables. They indicate that measuring the timing and persistence of kindergarten children's mathematics learning difficulties may help identify those most at risk for failing to become mathematically proficient during elementary school.

The severity of Minamata disease declined in 25 years: temporal profile of the neurological findings analyzed by multiple logistic regression model.

PubMed

Uchino, Makoto; Hirano, Teruyuki; Satoh, Hiroshi; Arimura, Kimiyoshi; Nakagawa, Masanori; Wakamiya, Jyunji

2005-01-01

Minamata disease (MD) was caused by ingestion of seafood from the methylmercury-contaminated areas. Although 50 years have passed since the discovery of MD, there have been only a few studies on the temporal profile of neurological findings in certified MD patients. Thus, we evaluated changes in neurological symptoms and signs of MD using discriminants by multiple logistic regression analysis. The severity of predictive index declined in 25 years in most of the patients. Only a few patients showed aggravation of neurological findings, which was due to complications such as spino-cerebellar degeneration. Patients with chronic MD aged over 45 years had several concomitant diseases so that their clinical pictures were complicated. It was difficult to differentiate chronic MD using statistically established discriminants based on sensory disturbance alone. In conclusion, the severity of MD declined in 25 years along with the modification by age-related concomitant disorders.

New Developments in the Embedded Statistical Coupling Method: Atomistic/Continuum Crack Propagation

NASA Technical Reports Server (NTRS)

Saether, E.; Yamakov, V.; Glaessgen, E.

2008-01-01

A concurrent multiscale modeling methodology that embeds a molecular dynamics (MD) region within a finite element (FEM) domain has been enhanced. The concurrent MD-FEM coupling methodology uses statistical averaging of the deformation of the atomistic MD domain to provide interface displacement boundary conditions to the surrounding continuum FEM region, which, in turn, generates interface reaction forces that are applied as piecewise constant traction boundary conditions to the MD domain. The enhancement is based on the addition of molecular dynamics-based cohesive zone model (CZM) elements near the MD-FEM interface. The CZM elements are a continuum interpretation of the traction-displacement relationships taken from MD simulations using Cohesive Zone Volume Elements (CZVE). The addition of CZM elements to the concurrent MD-FEM analysis provides a consistent set of atomistically-based cohesive properties within the finite element region near the growing crack. Another set of CZVEs are then used to extract revised CZM relationships from the enhanced embedded statistical coupling method (ESCM) simulation of an edge crack under uniaxial loading.

Coarse-Grained MD Simulations and Protein-Protein Interactions: The Cohesin-Dockerin System.

PubMed

Hall, Benjamin A; Sansom, Mark S P

2009-09-08

Coarse-grained molecular dynamics (CG-MD) may be applied as part of a multiscale modeling approach to protein-protein interactions. The cohesin-dockerin interaction provides a valuable test system for evaluation of the use of CG-MD, as structural (X-ray) data indicate a dual binding mode for the cohesin-dockerin pair. CG-MD simulations (of 5 μs duration) of the association of cohesin and dockerin identify two distinct binding modes, which resemble those observed in X-ray structures. For each binding mode, ca. 80% of interfacial residues are predicted correctly. Furthermore, each of the binding modes identified by CG-MD is conformationally stable when converted to an atomistic model and used as the basis of a conventional atomistic MD simulation of duration 20 ns.

Hypnosis in the Treatment of Major Depression: An Analysis of Heart Rate Variability.

PubMed

Chen, Xiuwen; Yang, Rongqian; Ge, Lulu; Luo, Jie; Lv, Ruixue

2017-01-01

Hypnosis is an adjuvant treatment of major depression (MD). Heart rate variability (HRV) can assess the autonomic nervous system, which is associated with MD, and HRV is decreased in MD patients. There is a lack of research on HRV changes before, during, and after the use of hypnosis in MD patients. A total of 21 MD patients participated in this study, and 5-minute electrocardiograms were recorded before, during, and after hypnosis. Compared with the prehypnotic condition, HRV parameters significantly (p < .01) increased in the hypnotic and posthypnotic conditions. The results suggest that hypnosis treatment should bring some functional improvement to the autonomic nervous system. HRV is potentially a useful tool that quantifies the physiological impact of hypnosis treatment in MD patients.

Maternal depression and infant development: theory and current evidence.

PubMed

Miklush, Lisa; Connelly, Cynthia D

2013-01-01

Maternal depression (MD) is a condition that has wide-ranging effects on the woman, her family, and the broader global society. It is generally agreed that MD is associated with untoward effects on the developmental trajectory of offspring. The aim of this article is to review the historical and theoretical underpinnings informing current thought linking MD with infant development, and to highlight some of the neuroendocrine and epigenetic processes related to MD and its sequelae. A broad understanding of the association between MD and infant developmental outcomes can inform nursing care of the childbearing family.

Using collective variables to drive molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Fiorin, Giacomo; Klein, Michael L.; Hénin, Jérôme

2013-12-01

A software framework is introduced that facilitates the application of biasing algorithms to collective variables of the type commonly employed to drive massively parallel molecular dynamics (MD) simulations. The modular framework that is presented enables one to combine existing collective variables into new ones, and combine any chosen collective variable with available biasing methods. The latter include the classic time-dependent biases referred to as steered MD and targeted MD, the temperature-accelerated MD algorithm, as well as the adaptive free-energy biases called metadynamics and adaptive biasing force. The present modular software is extensible, and portable between commonly used MD simulation engines.

hamlet, a binary genetic switch between single- and multiple- dendrite neuron morphology.

PubMed

Moore, Adrian W; Jan, Lily Yeh; Jan, Yuh Nung

2002-08-23

The dendritic morphology of neurons determines the number and type of inputs they receive. In the Drosophila peripheral nervous system (PNS), the external sensory (ES) neurons have a single nonbranched dendrite, whereas the lineally related multidendritic (MD) neurons have extensively branched dendritic arbors. We report that hamlet is a binary genetic switch between these contrasting morphological types. In hamlet mutants, ES neurons are converted to an MD fate, whereas ectopic hamlet expression in MD precursors results in transformation of MD neurons into ES neurons. Moreover, hamlet expression induced in MD neurons undergoing dendrite outgrowth drastically reduces arbor branching.

[Relationship between visual field index and visual field morphological stages of glaucoma and their diagnostic value].

PubMed

Hou, X R; Qin, J Y; Ren, Z Q

2017-02-11

Objective: To investigate the rationality of visual field morphological stages of glaucoma, its relationship with visual field index and their diagnostic value. Methods: Retrospective series case study. Two hundred and seventy-four glaucoma patients and 100 normal control received visual field examination by Humphrey perimeter using standard automatic perimetry (SAP) program from March 2014 to September 2014. Glaucoma patients were graded into four stages according to characteristic morphological damage of visual field, distribution of mean defect (MD) and visual field index (VFI) of each stage were plotted and receiver operation characteristic curve (ROC) was used to explore its correlation with MD and VFI. The diagnostic value of MD and VFI was also compared. For the comparison of general data of subjects, categorical variables were compared using χ(2) test, numerical variables were compared using F test. MD and VFI were compared using ANOVA among stages according to visual field, followed by multiple comparisons using LSD method. The correlation between MD and VFI and different stages according to visual field defined their diagnostic value, and compared using area under the curve (AUC) of ROC. Results: No characteristic visual field damage was found in normal control group, and MD and VFI was (-0.06±1.24) dB and (99.15±0.76)%, respectively. Glaucomatous visual field damage was graded into early, medium, late and end stage according to morphological characteristic. MD for each stage were (-2.83±2.00) dB, (-9.70±3.68) dB, (-18.46±2.90) dB, and (-27.96±2.76) dB, respectively. VFI for each stage were (93.84±3.61)%, (75.16±10.85)%, (49.36±11.26)% and (17.65±10.59)%, respectively. MD and VFI of each stage of glaucomatous group and normal control group were all significantly different ( F= 1 165.53 and P <0.01 for MD; F= 1 028.04 and P <0.01 for VFI). AUC of ROC was A(MD)=0.91 and Se(MD)=0.01 (95% confident interval was 0.89-0.94) for MD, and A(VFI)=0.97, Se(VFI)=0.01 (95% confident interval was 0.94-0.10) for VFI. So, AUC(VFI)>AUC(MD) ( P< 0.05). Conclusions: It is feasible and rational of glaucomatous visual field damage to be graded into early, medium, late and end stage using Humphrey perimeter. Distribution of MD and VFI for each stage was relatively concentrative. Both MD and VFI were useful for grading glaucomatous visual field damage with preference for VFI. (Chin J Ophthalmol, 2017, 53: 92-97) .

Properties of acid gels made from sodium caseinate-maltodextrin conjugates prepared by a wet heating method.

PubMed

Zhang, Shuwen; Gong, Yuansheng; Khanal, Som; Lu, Yanjie; Lucey, John A

2017-11-01

Covalent attachment of polysaccharides to proteins (conjugation) via the Maillard reaction has been extensively studied. Conjugation can lead to a significant improvement in protein functionality (e.g., solubility, emulsification, and heat stability). Caseins have previously been successfully conjugated with maltodextrin (Md), but the effect on the detailed acid gelation properties has not been examined. We studied the effect of conjugating sodium caseinate (NaCN) with 3 different sized Md samples via the Maillard reaction in aqueous solutions. The Md samples had dextrose equivalents of 4 to 7, 9 to 12, and 20 to 23 for Md40, Md100, and Md200, respectively. The conjugation reaction was performed in mixtures with 5% NaCN and 5% Md, which were heated at 90°C for 10 h. The degree of conjugation was estimated from the reduction in free amino groups as well as color changes. Sodium dodecyl sulfate-PAGE analysis was performed to confirm conjugation by employing staining of both protein and carbohydrate bands. The molar mass of samples was determined by size-exclusion chromatography coupled with multi-angle laser light scattering. After the conjugation reaction, samples were then gelled by the addition of 0.63% (wt/vol) glucono-δ-lactone at 30°C, such that samples reached pH 4.6 after about 13 h. The rheological properties of samples during acidification was monitored by small-strain dynamic oscillatory rheology. The microstructure of acid gels at pH 4.6 was examined by fluorescence microscopy. Conjugation resulted in a loss of 10.8, 8.8, and 11.9% of the available amino groups in the protein for the NaCN-Md40 conjugates (C40), NaCN-Md100 conjugates (C100), and NaCN-Md100 conjugates (C200), respectively. With a decrease in the size of the type of Md, an increase occurred in the molar mass of the resultant conjugate. The weight average molar masses of NaCN-Md samples were 340, 368, and 425 kDa for the conjugates C40, C100, and C200, respectively. Addition of Md to NaCN dispersion resulted in slightly shorter acid gelation times even without the conjugation reaction. The storage modulus (G') of acid gels was significantly lower in conjugated samples compared with the corresponding (unreacted) mixtures of Md and NaCN. The sample with the lowest G' value at pH 4.6 was the C40 conjugate. Fluorescence microscopy showed that gels made by conjugates had slightly larger pores. These results indicate that conjugation of casein modified its acid gelation properties, presumably by the Md polysaccharide moiety hindering aggregation and rearrangements of the casein network. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Muscular Dystrophy: Data and Statistics

MedlinePlus

... For… Media Policy Makers MD STARnet Data and Statistics Recommend on Facebook Tweet Share Compartir Expand All Collapse All The following data and statistics come from MD STARnet. Data from the MD ...

An unusual plant triterpene synthase with predominant α-amyrin-producing activity identified by characterizing oxidosqualene cyclases from Malus × domestica.

PubMed

Brendolise, Cyril; Yauk, Yar-Khing; Eberhard, Ellen D; Wang, Mindy; Chagne, David; Andre, Christelle; Greenwood, David R; Beuning, Lesley L

2011-07-01

The pentacyclic triterpenes, in particular ursolic acid and oleanolic acid and their derivatives, exist abundantly in the plant kingdom, where they are well known for their anti-inflammatory, antitumour and antimicrobial properties. α-Amyrin and β-amyrin are the precursors of ursolic and oleanolic acids, respectively, formed by concerted cyclization of squalene epoxide by a complex synthase reaction. We identified three full-length expressed sequence tag sequences in cDNA libraries constructed from apple (Malus × domestica 'Royal Gala') that were likely to encode triterpene synthases. Two of these expressed sequence tag sequences were essentially identical (> 99% amino acid similarity; MdOSC1 and MdOSC3). MdOSC1 and MdOSC2 were expressed by transient expression in Nicotiana benthamiana leaves and by expression in the yeast Pichia methanolica. The resulting products were analysed by GC and GC-MS. MdOSC1 was shown to be a mixed amyrin synthase (a 5 : 1 ratio of α-amyrin to β-amyrin). MdOSC1 is the only triterpene synthase so far identified in which the level of α-amyrin produced is > 80% of the total product and is, therefore, primarily an α-amyrin synthase. No product was evident for MdOSC2 when expressed either transiently or in yeast, suggesting that this putative triterpene synthase is either encoded by a pseudogene or does not express well in these systems. Transcript expression analysis in Royal Gala indicated that the genes are mostly expressed in apple peel, and that the MdOSC2 expression level was much lower than that of MdOSC1 and MdOSC3 in all the tissues tested. Amyrin content analysis was undertaken by LC-MS, and demonstrated that levels and ratios differ between tissues, but that the true consequence of synthase activity is reflected in the ursolic/oleanolic acid content and in further triterpenoids derived from them. Phylogenetic analysis placed the three triterpene synthase sequences with other triterpene synthases that encoded either α-amyrin and/or β-amyrin synthase. MdOSC1 and MdOSC3 clustered with the multifunctional triterpene synthases, whereas MdOSC2 was most similar to the β-amyrin synthases. © 2011 The New Zealand Institute for Plant and Food Research Limited. Journal compilation © 2011 FEBS.

Host Genetics and Vaccine Efficacy: Global gene expression differentiation induced by vaccine and MDV in MD resistant and susceptible chickens based on Next-Gen RNA-Seq reads

USDA-ARS?s Scientific Manuscript database

Marek’s disease (MD) is a herpesvirus-induced disease of poultry and it continues to threaten the poultry industry worldwide as MD virus (MDV) evolves to escalate the virulence of field strains. MD has been primarily controlled by vaccination and management measures. This study aimed to compare the ...

78 FR 32556 - Safety Zone; 2013 Ocean City Air Show, Atlantic Ocean; Ocean City, MD

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-31

...-AA00 Safety Zone; 2013 Ocean City Air Show, Atlantic Ocean; Ocean City, MD AGENCY: Coast Guard, DHS... navigable waters of the Atlantic Ocean in the vicinity of Ocean City, MD to support the Ocean City Air Show... June 9, 2013, Ocean City, MD will host an air show event between Talbot Street and 33rd Street over the...

The health care response to pandemic influenza.

PubMed

Barnitz, Laura; Berkwits, Michael

2006-07-18

The threat of an H5N1 influenza virus (avian flu) pandemic is substantial. The success of the current U.S. influenza pandemic response plan depends on effective coordination among state and local public health authorities and individual health care providers. This article is a summary of a public policy paper developed by the American College of Physicians to address issues in the U.S. Department of Health and Human Services Pandemic Influenza Plan that involve physicians. The College's positions call for the following: 1) development of local public health task forces that include physicians representing all specialties and practice settings; 2) physician access to 2-way communication with public health authorities and to information technology tools for diagnosis and syndrome surveillance; 3) clear identification and authorization of agencies to process licensing and registration of volunteer physicians; 4) clear guidelines for overriding standard procedures for confidentiality and consent in the interest of the public's health; 5) clear and fair infection control measures that do not create barriers to care; 6) analysis of and solutions to current problems with seasonal influenza vaccination programs as a way of developing a maximally efficient pandemic flu vaccine program; 7) federal funding to provide pandemic flu vaccine for the entire U.S. population and antiviral drugs for 25% of the population; and 8) planning for health care in alternative, nonhospital settings to prevent a surge in demand for hospital care that exceeds supply. *This paper is an abridged version of a full-text position paper (available at http://www.acponline.org/college/pressroom/as06/pandemic_policy.pdf) written by Laura Barnitz, BJ, MA, and updated and adapted for publication in Annals of Internal Medicine by Michael Berkwits, MD, MSCE. The original position paper was developed for the Health and Public Policy Committee of the American College of Physicians: Jeffrey P. Harris, MD (Chair); David L. Bronson, MD (Vice Chair); CPT Julie Ake, MD; Patricia P. Barry, MD; Molly Cooke, MD; Herbert S. Diamond, MD; Joel S. Levine, MD; Mark E. Mayer, MD; Thomas McGinn, MD; Robert M. McLean, MD; Ashley E. Starkweather; and Frederick E. Turton, MD. It was approved by the Board of Regents on 3 April 2006.

Comparison of sediment and nutrient export and runoff characteristics from watersheds with centralized versus distributed stormwater management

USGS Publications Warehouse

Hopkins, Kristina G.; Loperfido, J.V.; Craig, Laura S.; Noe, Gregory; Hogan, Dianna

2017-01-01

Stormwater control measures (SCMs) are used to retain stormwater and pollutants. SCMs have traditionally been installed in a centralized manner using detention to mitigate peak flows. Recently, distributed SCM networks that treat runoff near the source have been increasingly utilized. The aim of this study was to evaluate differences among watersheds that vary in SCM arrangement by assessing differences in baseflow nutrient (NOx-N and PO4−) concentrations and fluxes, stormflow export of suspended sediments and particulate phosphorus (PP), and runoff characteristics. A paired watershed approach was used to compare export between 2004 and 2016 from one forested watershed (For-MD), one suburban watershed with centralized SCMs (Cent-MD), and one suburban watershed with distributed SCMs (Dist-MD). Results indicated baseflow nitrate (NOx-N) concentrations typically exceeded 1 mg-N/L in all watersheds and were highest in Dist-MD. Over the last 10 years in Dist-MD, nitrate concentrations in both stream baseflow and in a groundwater well declined as land use shifted from agriculture to suburban. Baseflow nitrate export temporarily increased during the construction phase of SCM development in Dist-MD. This temporary pulse of nitrate may be attributed to the conversion of sediment control facilities to SCMs and increased subsurface flushing as infiltration SCMs came on line. During storm flow, Dist-MD tended to have less runoff and lower maximum specific discharge than Cent-MD for small events (<1.3 cm), but runoff responses became increasingly similar to Cent-MD with increasing precipitation (>1.3 cm). Mass export estimated during paired storm events indicated Dist-MD exported 30% less sediment and 31% more PP than Cent-MD. For large precipitation events, export of sediment and PP was similar among all three watersheds. Results suggest that distributed SCMs can reduce runoff and sediment loads during small rain events compared to centralized SCMs, but these differences become less evident for large events when peak discharge likely leads to substantial bank erosion.

Enhanced configurational sampling with hybrid non-equilibrium molecular dynamics-Monte Carlo propagator

NASA Astrophysics Data System (ADS)

Suh, Donghyuk; Radak, Brian K.; Chipot, Christophe; Roux, Benoît

2018-01-01

Molecular dynamics (MD) trajectories based on classical equations of motion can be used to sample the configurational space of complex molecular systems. However, brute-force MD often converges slowly due to the ruggedness of the underlying potential energy surface. Several schemes have been proposed to address this problem by effectively smoothing the potential energy surface. However, in order to recover the proper Boltzmann equilibrium probability distribution, these approaches must then rely on statistical reweighting techniques or generate the simulations within a Hamiltonian tempering replica-exchange scheme. The present work puts forth a novel hybrid sampling propagator combining Metropolis-Hastings Monte Carlo (MC) with proposed moves generated by non-equilibrium MD (neMD). This hybrid neMD-MC propagator comprises three elementary elements: (i) an atomic system is dynamically propagated for some period of time using standard equilibrium MD on the correct potential energy surface; (ii) the system is then propagated for a brief period of time during what is referred to as a "boosting phase," via a time-dependent Hamiltonian that is evolved toward the perturbed potential energy surface and then back to the correct potential energy surface; (iii) the resulting configuration at the end of the neMD trajectory is then accepted or rejected according to a Metropolis criterion before returning to step 1. A symmetric two-end momentum reversal prescription is used at the end of the neMD trajectories to guarantee that the hybrid neMD-MC sampling propagator obeys microscopic detailed balance and rigorously yields the equilibrium Boltzmann distribution. The hybrid neMD-MC sampling propagator is designed and implemented to enhance the sampling by relying on the accelerated MD and solute tempering schemes. It is also combined with the adaptive biased force sampling algorithm to examine. Illustrative tests with specific biomolecular systems indicate that the method can yield a significant speedup.

Enhanced configurational sampling with hybrid non-equilibrium molecular dynamics-Monte Carlo propagator.

PubMed

Suh, Donghyuk; Radak, Brian K; Chipot, Christophe; Roux, Benoît

2018-01-07

Molecular dynamics (MD) trajectories based on classical equations of motion can be used to sample the configurational space of complex molecular systems. However, brute-force MD often converges slowly due to the ruggedness of the underlying potential energy surface. Several schemes have been proposed to address this problem by effectively smoothing the potential energy surface. However, in order to recover the proper Boltzmann equilibrium probability distribution, these approaches must then rely on statistical reweighting techniques or generate the simulations within a Hamiltonian tempering replica-exchange scheme. The present work puts forth a novel hybrid sampling propagator combining Metropolis-Hastings Monte Carlo (MC) with proposed moves generated by non-equilibrium MD (neMD). This hybrid neMD-MC propagator comprises three elementary elements: (i) an atomic system is dynamically propagated for some period of time using standard equilibrium MD on the correct potential energy surface; (ii) the system is then propagated for a brief period of time during what is referred to as a "boosting phase," via a time-dependent Hamiltonian that is evolved toward the perturbed potential energy surface and then back to the correct potential energy surface; (iii) the resulting configuration at the end of the neMD trajectory is then accepted or rejected according to a Metropolis criterion before returning to step 1. A symmetric two-end momentum reversal prescription is used at the end of the neMD trajectories to guarantee that the hybrid neMD-MC sampling propagator obeys microscopic detailed balance and rigorously yields the equilibrium Boltzmann distribution. The hybrid neMD-MC sampling propagator is designed and implemented to enhance the sampling by relying on the accelerated MD and solute tempering schemes. It is also combined with the adaptive biased force sampling algorithm to examine. Illustrative tests with specific biomolecular systems indicate that the method can yield a significant speedup.

Efficient hybrid non-equilibrium molecular dynamics--Monte Carlo simulations with symmetric momentum reversal.

PubMed

Chen, Yunjie; Roux, Benoît

2014-09-21

Hybrid schemes combining the strength of molecular dynamics (MD) and Metropolis Monte Carlo (MC) offer a promising avenue to improve the sampling efficiency of computer simulations of complex systems. A number of recently proposed hybrid methods consider new configurations generated by driving the system via a non-equilibrium MD (neMD) trajectory, which are subsequently treated as putative candidates for Metropolis MC acceptance or rejection. To obey microscopic detailed balance, it is necessary to alter the momentum of the system at the beginning and/or the end of the neMD trajectory. This strict rule then guarantees that the random walk in configurational space generated by such hybrid neMD-MC algorithm will yield the proper equilibrium Boltzmann distribution. While a number of different constructs are possible, the most commonly used prescription has been to simply reverse the momenta of all the particles at the end of the neMD trajectory ("one-end momentum reversal"). Surprisingly, it is shown here that the choice of momentum reversal prescription can have a considerable effect on the rate of convergence of the hybrid neMD-MC algorithm, with the simple one-end momentum reversal encountering particularly acute problems. In these neMD-MC simulations, different regions of configurational space end up being essentially isolated from one another due to a very small transition rate between regions. In the worst-case scenario, it is almost as if the configurational space does not constitute a single communicating class that can be sampled efficiently by the algorithm, and extremely long neMD-MC simulations are needed to obtain proper equilibrium probability distributions. To address this issue, a novel momentum reversal prescription, symmetrized with respect to both the beginning and the end of the neMD trajectory ("symmetric two-ends momentum reversal"), is introduced. Illustrative simulations demonstrate that the hybrid neMD-MC algorithm robustly yields a correct equilibrium probability distribution with this prescription.

Efficient hybrid non-equilibrium molecular dynamics - Monte Carlo simulations with symmetric momentum reversal

NASA Astrophysics Data System (ADS)

Chen, Yunjie; Roux, Benoît

2014-09-01

Hybrid schemes combining the strength of molecular dynamics (MD) and Metropolis Monte Carlo (MC) offer a promising avenue to improve the sampling efficiency of computer simulations of complex systems. A number of recently proposed hybrid methods consider new configurations generated by driving the system via a non-equilibrium MD (neMD) trajectory, which are subsequently treated as putative candidates for Metropolis MC acceptance or rejection. To obey microscopic detailed balance, it is necessary to alter the momentum of the system at the beginning and/or the end of the neMD trajectory. This strict rule then guarantees that the random walk in configurational space generated by such hybrid neMD-MC algorithm will yield the proper equilibrium Boltzmann distribution. While a number of different constructs are possible, the most commonly used prescription has been to simply reverse the momenta of all the particles at the end of the neMD trajectory ("one-end momentum reversal"). Surprisingly, it is shown here that the choice of momentum reversal prescription can have a considerable effect on the rate of convergence of the hybrid neMD-MC algorithm, with the simple one-end momentum reversal encountering particularly acute problems. In these neMD-MC simulations, different regions of configurational space end up being essentially isolated from one another due to a very small transition rate between regions. In the worst-case scenario, it is almost as if the configurational space does not constitute a single communicating class that can be sampled efficiently by the algorithm, and extremely long neMD-MC simulations are needed to obtain proper equilibrium probability distributions. To address this issue, a novel momentum reversal prescription, symmetrized with respect to both the beginning and the end of the neMD trajectory ("symmetric two-ends momentum reversal"), is introduced. Illustrative simulations demonstrate that the hybrid neMD-MC algorithm robustly yields a correct equilibrium probability distribution with this prescription.

Cigarette smoking and mammographic density in the Danish Diet, Cancer and Health cohort.

PubMed

Jacobsen, Katja Kemp; Lynge, Elsebeth; Vejborg, Ilse; Tjønneland, Anne; von Euler-Chelpin, My; Andersen, Zorana J

2016-02-01

Smoking before first childbirth increases breast cancer risk, but the biological mechanism remains unknown and may involve mammographic density (MD), one of the strongest biomarkers of breast cancer risk. We aimed to examine whether active smoking and passive smoking were associated with MD. For the 5,356 women (4,489 postmenopausal) from the Danish Diet, Cancer and Health cohort (1993-1997) who attended mammographic screening in Copenhagen (1993-2001), we used MD (mixed/dense or fatty) assessed at the first screening after cohort entry. Active smoking (status, duration, and intensity) and passive smoking were assessed at cohort baseline (1993-1997) via questionnaire, together with other breast cancer risk factors. Logistic regression was used to estimate associations (odds ratios, 95 % confidence intervals) between smoking and MD, adjusting for confounders. Two thousand and twenty-six (56.5 %) women had mixed/dense MD, 2,214 (41.4 %) were current, and 1,175 (21.9 %) former smokers. Current smokers had significantly lower odds (0.86, 0.75-0.99) of having mixed/dense MD compared to never smokers, while former smoking was not associated with MD. Inverse association between smoking and MD was strongest in women who initiated smoking before age of 16 years (0.79, 0.64-0.96), smoked ≥15 cigarettes/day (0.83, 0.71-0.98), smoked ≥5 pack-years (0.62, 0.43-0.89), smoked >30 years (0.86, 0.75-0.99), and smoked ≥11 years before first childbirth (0.70, 0.51-0.96). Association between smoking and MD diminished after smoking cessation, with increased odds of having mixed/dense breasts in women who quit smoking >20 years ago as compared to current smokers (1.37, 1.01-1.67). There was no association between passive smoking and MD. We found an inverse association between active smoking and MD.

Expression levels of uridine 5'-diphospho-glucuronosyltransferase genes in breast tissue from healthy women are associated with mammographic density.

PubMed

Haakensen, Vilde D; Biong, Margarethe; Lingjærde, Ole Christian; Holmen, Marit Muri; Frantzen, Jan Ole; Chen, Ying; Navjord, Dina; Romundstad, Linda; Lüders, Torben; Bukholm, Ida K; Solvang, Hiroko K; Kristensen, Vessela N; Ursin, Giske; Børresen-Dale, Anne-Lise; Helland, Aslaug

2010-01-01

Mammographic density (MD), as assessed from film screen mammograms, is determined by the relative content of adipose, connective and epithelial tissue in the female breast. In epidemiological studies, a high percentage of MD confers a four to six fold risk elevation of developing breast cancer, even after adjustment for other known breast cancer risk factors. However, the biologic correlates of density are little known. Gene expression analysis using whole genome arrays was performed on breast biopsies from 143 women; 79 women with no malignancy (healthy women) and 64 newly diagnosed breast cancer patients, both included from mammographic centres. Percent MD was determined using a previously validated, computerized method on scanned mammograms. Significance analysis of microarrays (SAM) was performed to identify genes influencing MD and a linear regression model was used to assess the independent contribution from different variables to MD. SAM-analysis identified 24 genes differentially expressed between samples from breasts with high and low MD. These genes included three uridine 5'-diphospho-glucuronosyltransferase (UGT) genes and the oestrogen receptor gene (ESR1). These genes were down-regulated in samples with high MD compared to those with low MD. The UGT gene products, which are known to inactivate oestrogen metabolites, were also down-regulated in tumour samples compared to samples from healthy individuals. Several single nucleotide polymorphisms (SNPs) in the UGT genes associated with the expression of UGT and other genes in their vicinity were identified. Three UGT enzymes were lower expressed both in breast tissue biopsies from healthy women with high MD and in biopsies from newly diagnosed breast cancers. The association was strongest amongst young women and women using hormonal therapy. UGT2B10 predicts MD independently of age, hormone therapy and parity. Our results indicate that down-regulation of UGT genes in women exposed to female sex hormones is associated with high MD and might increase the risk of breast cancer.

Expression levels of uridine 5'-diphospho-glucuronosyltransferase genes in breast tissue from healthy women are associated with mammographic density

PubMed Central

2010-01-01

Introduction Mammographic density (MD), as assessed from film screen mammograms, is determined by the relative content of adipose, connective and epithelial tissue in the female breast. In epidemiological studies, a high percentage of MD confers a four to six fold risk elevation of developing breast cancer, even after adjustment for other known breast cancer risk factors. However, the biologic correlates of density are little known. Methods Gene expression analysis using whole genome arrays was performed on breast biopsies from 143 women; 79 women with no malignancy (healthy women) and 64 newly diagnosed breast cancer patients, both included from mammographic centres. Percent MD was determined using a previously validated, computerized method on scanned mammograms. Significance analysis of microarrays (SAM) was performed to identify genes influencing MD and a linear regression model was used to assess the independent contribution from different variables to MD. Results SAM-analysis identified 24 genes differentially expressed between samples from breasts with high and low MD. These genes included three uridine 5'-diphospho-glucuronosyltransferase (UGT) genes and the oestrogen receptor gene (ESR1). These genes were down-regulated in samples with high MD compared to those with low MD. The UGT gene products, which are known to inactivate oestrogen metabolites, were also down-regulated in tumour samples compared to samples from healthy individuals. Several single nucleotide polymorphisms (SNPs) in the UGT genes associated with the expression of UGT and other genes in their vicinity were identified. Conclusions Three UGT enzymes were lower expressed both in breast tissue biopsies from healthy women with high MD and in biopsies from newly diagnosed breast cancers. The association was strongest amongst young women and women using hormonal therapy. UGT2B10 predicts MD independently of age, hormone therapy and parity. Our results indicate that down-regulation of UGT genes in women exposed to female sex hormones is associated with high MD and might increase the risk of breast cancer. PMID:20799965

Epigenetic regulation of MdMYB1 is associated with paper bagging-induced red pigmentation of apples.

PubMed

Bai, Songling; Tuan, Pham Anh; Saito, Takanori; Honda, Chikako; Hatsuyama, Yoshimichi; Ito, Akiko; Moriguchi, Takaya

2016-09-01

Paper-bagging treatment can transform non-transcribed MdMYB1 - 2 and MdMYB1 - 3 alleles into transcribed alleles through epigenetic regulations, resulting in the red pigmentation of a normally non-red apple cultivar 'Mutsu.' Anthocyanin biosynthesis in apples is regulated by MdMYB1/A/10, an R2R3-Type MYB gene. 'Mutsu,' a triploid apple cultivar harboring non-transcribed MdMYB1-2 and MdMYB1-3 alleles, retains green skin color under field conditions. However, it can show red/pink pigmentation under natural or artificial ultraviolet-B (UV-B) light exposure after paper-bagging and bag removal treatment. In the present study, we found that in 'Mutsu,' paper bagging-induced red pigmentation was due to the activation of non-transcribed MdMYB1-2/-3 alleles, which triggered the expression of downstream anthocyanin biosynthesis genes in a UV-B-dependent manner. By monitoring the epigenetic changes during UV-B-induced pigmentation, no significant differences in DNA methylation and histone modifications in the 5' upstream region of MdMYB1-2/-3 were recorded between the UV-B-treated fruit skin (red) and the fruit skin treated only by white light (green). In contrast, bag treatment lowered the DNA methylation in this region of MdMYB1-2/-3 alleles. Similarly, higher levels of histone H3 acetylation and trimethylation of H3 tail at lysine 4, and lower level of trimethylation of H3 tail at lysine 27 were observed in the 5' upstream region of MdMYB1-2/-3 in the skin of the fruit immediately after bag removal. These results suggest that bagging treatment can induce epigenetic changes, facilitating the binding of trans factor(s) to MdMYB1-2/-3 alleles, resulting in the activation of these MYBs after bag removal.

Effects of Twenty Days of the Ketogenic Diet on Metabolic and Respiratory Parameters in Healthy Subjects.

PubMed

Rubini, Alessandro; Bosco, Gerardo; Lodi, Alessandra; Cenci, Lorenzo; Parmagnani, Andrea; Grimaldi, Keith; Zhongjin, Yang; Paoli, Antonio

2015-12-01

The effects of the ketogenic diet (KD) on weight loss, metabolic, and respiratory parameters were investigated in healthy subjects. Thirty-two healthy subjects were randomized into two groups. The KD group followed a ketogenic diet for 20 days (KD t 0-t 20), then switched to a low-carbohydrate, no-ketogenic diet for 20 days (KD t 20-t 40), and finally was on a Mediterranean diet (MD) for 2 more months (KD t 40-t 2m). The MD group followed a MD for 20 days (MD t 0-t 20), then followed a MD of 1400 kcal over the next 20 days (MD t 20-t 40), and completed the study with the MD for 2 months (MD t 40-t 2m). Body weight, body fat, respiratory rate, and respiratory gas parameters (including respiratory exchange ratio (RER) and carbon dioxide end-tidal partial pressure (PETCO2), oxygen uptake (VO2), carbon dioxide production (VCO2), and resting energy expenditure (REE)) were measured at each point. A significant decrease (p < 0.05) in RER was observed after 20 and 40 days in the KD group, but not in the MD group. In the KD group, significant reductions were observed for both carbon dioxide output and PETCO2, however, there was no significant change in VO2, VCO2, and REE. While both diets significantly decreased body fat mass, the KD diet overall proved to have a higher percentage of fat loss versus the MD diet. The KD may significantly decrease carbon dioxide body stores, which may theoretically be beneficial for patients with increased carbon dioxide arterial partial pressure due to respiratory insufficiency or failure.

The Mediterranean diet among British older adults: Its understanding, acceptability and the feasibility of a randomised brief intervention with two levels of dietary advice.

PubMed

Lara, Jose; Turbett, Edel; Mckevic, Agata; Rudgard, Kate; Hearth, Henrietta; Mathers, John C

2015-12-01

To assess (i) understanding, acceptability and preference for two graphical displays of the Mediterranean diet (MD); and (ii) feasibility of a brief MD intervention and cost of adherence to this diet among British older adults. Two studies undertaken at the Human Nutrition Research Centre, Newcastle University are reported. In study-1, preference and understanding of the MD guidelines and two graphical displays, a plate and a pyramid, were evaluated in an educational group session (EGS). In study-2, we evaluated the feasibility of a three-week brief MD intervention with two levels of dietary advice: Group-1 (level 1) attended an EGS on the MD, and Group-2 (level 2) attended an EGS and received additional support. MD adherence using a 9-point score, and the cost of food intake during intervention, were assessed. RESULTS STUDY-1: No differences in preference for a MD plate or pyramid were observed. Both graphic displays were rated as acceptable and conveyed clearly these guidelines. STUDY-2: The intervention was rated as acceptable. No significant differences were observed between groups 1 and 2. Analysis of the combined sample showed significant increases from baseline in fish intake (P=0.01) and MD score (P=0.05). The cost of food intake during intervention was not significantly different from baseline. British older adults rated a MD as an acceptable model of healthy eating, and a plate and a pyramid as comprehensible graphic displays of these guidelines. A brief dietary intervention was also acceptable and revealed that greater adherence to the MD could be achieved without incurring significantly greater costs. Copyright © 2015. Published by Elsevier Ireland Ltd.

Clinical Value of Vestibular Evoked Myogenic Potential in Assessing the Stage and Predicting the Hearing Results in Ménière's Disease

PubMed Central

Kim, Min-Beom; Choi, Jeesun; Park, Ga Young; Cho, Yang-Sun; Hong, Sung Hwa

2013-01-01

Objectives Our goal was to find the clinical value of cervical vestibular evoked myogenic potential (VEMP) in Ménière's disease (MD) and to evaluate whether the VEMP results can be useful in assessing the stage of MD. Furthermore, we tried to evaluate the clinical effectiveness of VEMP in predicting hearing outcomes. Methods The amplitude, peak latency and interaural amplitude difference (IAD) ratio were obtained using cervical VEMP. The VEMP results of MD were compared with those of normal subjects, and the MD stages were compared with the IAD ratio. Finally, the hearing changes were analyzed according to their VEMP results. Results In clinically definite unilateral MD (n=41), the prevalence of cervical VEMP abnormality in the IAD ratio was 34.1%. When compared with normal subjects (n=33), the VEMP profile of MD patients showed a low amplitude and a similar latency. The mean IAD ratio in MD was 23%, which was significantly different from that of normal subjects (P=0.01). As the stage increased, the IAD ratio significantly increased (P=0.09). After stratification by initial hearing level, stage I and II subjects (hearing threshold, 0-40 dB) with an abnormal IAD ratio showed a decrease in hearing over time compared to those with a normal IAD ratio (P=0.08). Conclusion VEMP parameters have an important clinical role in MD. Especially, the IAD ratio can be used to assess the stage of MD. An abnormal IAD ratio may be used as a predictor of poor hearing outcomes in subjects with early stage MD. PMID:23799160

Tests of causal links between alcohol abuse or dependence and major depression.

PubMed

Fergusson, David M; Boden, Joseph M; Horwood, L John

2009-03-01

There has been a great deal of research on the comorbidity between alcohol abuse or dependence (AAD) and major depression (MD). However, it is unclear whether AAD increases the risk of MD or vice versa. To examine the associations between AAD and MD using fixed-effects modeling to control for confounding and using structural equation models to ascertain the direction of causality. Data were gathered during the course of the Christchurch Health and Development Study, a 25-year longitudinal study of a birth cohort of children from New Zealand (635 boys, 630 girls). General community sample. The analysis was based on a sample of 1055 participants with available data on AAD and MD at ages 17 to 18, 20 to 21, and 24 to 25 years. Symptom criteria for AAD and MD from the DSM-IV at ages 17 to 18, 20 to 21, and 24 to 25 years as well as measures of life stress, cannabis use, other illicit drug use, affiliation with deviant peers, unemployment, partner substance use, and partner criminality at ages 17 to 18, 20 to 21, and 24 to 25 years. There were significant (P < .001) pooled associations between AAD and MD. Controlling for confounding factors using conditional fixed-effects models and time-dynamic covariate factors reduced the magnitude of these associations, but they remained statistically significant. Structural equation modeling suggested that the best-fitting causal model was one in which AAD led to increased risk of MD. The findings suggest that the associations between AAD and MD were best explained by a causal model in which problems with alcohol led to increased risk of MD as opposed to a self-medication model in which MD led to increased risk of AAD.

Cancer Data and Statistics Tools

MedlinePlus

... Joseph Jacqueline W. Miller Mona Saraiya Judith Lee Smith Sherri L. Stewart Mary C. White Debra Younginer ... MD, MPH Simple Singh, MD, MPH Judith Lee Smith, PhD Sherri L. Stewart, PhD Eric Tai, MD, ...

Impact of Migraine on School Performance

MedlinePlus

... Spencer, MD Steven Karceski, MD The impact of migraine on school performance Daniel Kantor, MD e168 WHAT ... this study tackle an often overlooked problem: how migraine headache affects the school performance of children. 1 ...

Inhibition of low-density lipoprotein oxidation by Nagano purple grape (Vitis viniferaxVitis labrusca).

PubMed

Kamiyama, Masumi; Kishimoto, Yoshimi; Tani, Mariko; Andoh, Kunihiko; Utsunomiya, Kazunori; Kondo, Kazuo

2009-12-01

The Nagano Purple grape (Vitis (V.) viniferaxV. labrusca) is a hybrid created by a cross between Kyoho (V. viniferaxV. labrusca) and Rosario Bianco (V. vinifera) grapes. The grape, including its skin, can be eaten and contains no seeds because of gibberellin treatment. The skins of various fruits have been shown to contain antioxidant activity. However, it is unclear whether the Nagano Purple grape contains antioxidant activity. We prepared the skins and dried fruits (including the skins) of the Nagano Purple grape, so as to assay for the presence of an antioxidant activity. We examined the concentration of polyphenols in the grape and further assayed whether components in the grape inhibited the oxidation of low-density lipoprotein (LDL). We detected the presence of cyanidin-3-glucoside (Cy-3-glc), five anthocyanidins and resveratrol in the skins. A trace of resveratrol was detected in the pulp. LDL collected from human subjects 1 h following the consumption of the skins or dried fruits revealed significant inhibition of LDL oxidation compared to that observed in fasting venous blood samples. We further observed the antioxidant activity of Cy-3-glc. Our results suggest that the consumption of the Nagano Purple grape can give rise to resistance to LDL oxidation.

Muscle dysmorphia in Hungarian non-competitive male bodybuilders.

PubMed

Babusa, B; Túry, F

2012-03-01

Muscle dysmorphia (MD) has been described as a male body image disorder, characterized by a pathological preoccupation with muscle size. The aim of the study was to examine the MD features, eating disorder characteristics and body attitudes in non-competitive male bodybuilders in a Hungarian sample. Sixty male bodybuilders and 60 undergraduate university students completed the self-report questionnaires of the Muscle Appearance Satisfaction Scale, the Body Attitude Test and the Eating Disorders Inventory. MD was associated with current bodybuilding activity, higher ideal body weight and eating disorder characteristics. Moreover, current selfreported steroid users displayed higher tendency for MD symptoms than self-reported steroid non-users. Results emphasize the relationship between MD symptoms, eating disorder characteristics and steroid use. MD and body image related concerns among men could be a wide-spread phenomena also in the Central-Eastern European region.

The pathology of methylmercury poisoning (Minamata disease): The 50th Anniversary of Japanese Society of Neuropathology.

PubMed

Eto, Komyo; Marumoto, Masumi; Takeya, Motohiro

2010-10-01

Methylmercury (Me-Hg) poisoning (Minamata disease: MD) is one of the most severe types of disease caused by humans to humans in Japan. The disease is a special class of food-borne methylmercury intoxication in humans as typified by the outbreak that began in 1953 in Minamata and its vicinity in Kumamoto Prefecture, Japan. There are 450 autopsy cases in Kumamoto and 30 autopsy cases in Niigata Prefecture related to MD in Japan. Two hundred and one cases in Kumamoto and 22 cases in Niigata showed pathological changes of MD. This report provides a brief research history and overview of the pathological changes of MD, and also presents representative cases of adult, infantile and fetal forms of MD among the 450 MD-related autopsy cases in Kumamoto Prefecture. © 2010 Japanese Society of Neuropathology.

MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study.

PubMed

Tourbah, Ayman; Lebrun-Frenay, Christine; Edan, Gilles; Clanet, Michel; Papeix, Caroline; Vukusic, Sandra; De Sèze, Jerome; Debouverie, Marc; Gout, Olivier; Clavelou, Pierre; Defer, Gilles; Laplaud, David-Axel; Moreau, Thibault; Labauge, Pierre; Brochet, Bruno; Sedel, Frédéric; Pelletier, Jean

2016-11-01

Treatment with MD1003 (high-dose biotin) showed promising results in progressive multiple sclerosis (MS) in a pilot open-label study. To confirm the efficacy and safety of MD1003 in progressive MS in a double-blind, placebo-controlled study. Patients (n = 154) with a baseline Expanded Disability Status Scale (EDSS) score of 4.5-7 and evidence of disease worsening within the previous 2 years were randomised to 12-month MD1003 (100 mg biotin) or placebo thrice daily, followed by 12-month MD1003 for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6-7) or a ⩾20% decrease in timed 25-foot walk time compared with the best baseline among screening or randomisation visits. A total of 13 (12.6%) MD1003-treated patients achieved the primary endpoint versus none of the placebo-treated patients (p = 0.005). MD1003 treatment also reduced EDSS progression and improved clinical impression of change compared with placebo. Efficacy was maintained over follow-up, and the safety profile of MD1003 was similar to that of placebo. MD1003 achieves sustained reversal of MS-related disability in a subset of patients with progressive MS and is well tolerated. © The Author(s), 2016.

Identification of a xyloglucan-specific endo-(1-4)-beta-D-glucanase inhibitor protein from apple (Malus × domestica Borkh.) as a potential defense gene against Botryosphaeria dothidea.

PubMed

Bai, Suhua; Dong, Chaohua; Zhu, Jun; Zhang, Yugang; Dai, Hongyi

2015-02-01

Botryosphaeria dothidea is the causal agent of apple ring rot which is a highly destructive apple disease in China. Here, a putative xyloglucan-specific endo-(1-4)-beta-d-glucanase inhibitor protein from Malus×domestica (designated as MdXEGIP1) was found to be involved in defense against B. dothidea infection. MdXEGIP1 shares high amino acid sequence identity with other apple XEGIPs, but exhibited significantly different responses to B. dothidea infection. Quantitative real-time PCR revealed that MdXEGIP1 expression was significantly induced in shoot bark of apple plant by B. dothidea and showed different expression pattern in resistant and susceptible apple cultivars. In resistant cultivar, MdXEGIP1 expression was elevated with larger amplitude than that in susceptible cultivar after B. dothidea infection. MdXEGIP1 expression was also significantly enhanced by treatment with exogenous methyl jasmonate and salicylic acid in apple plantlets. Further investigation revealed that recombinant MdXEGIP1 has significant inhibitor activity to XEGs from family 12 and 74 of glycoside hydrolase. More importantly, recombinant MdXEGIP1 inhibited crude enzyme solution of XEG from B. dothidea, suggesting that MdXEGIP1 might protect apple plant from B. dothidea infection by inhibiting XEG activity. Taken together, the results indicated that MdXEGIP1 is a potential defense gene against B. dothidea in apple. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Childhood Trauma and Minimization/Denial in People with and without a Severe Mental Disorder.

PubMed

Church, Chelsea; Andreassen, Ole A; Lorentzen, Steinar; Melle, Ingrid; Aas, Monica

2017-01-01

Background: Childhood trauma has garnered extensive research concerning its role in the psychopathology of mental disorders, including psychosis. The Childhood Trauma Questionnaire (CTQ) utilizes a minimization/denial (MD) scale to denote potential under-reporters of trauma, yet MD scores are infrequently reported and validations of the scale are lacking in the literature. Elucidate differences in MD between patients with severe mental disorders to healthy individuals, and secondly, investigate if MD influences reports of childhood trauma between the groups. Methods: We included 621 patients with a DSM-schizophrenia spectrum, bipolar spectrum diagnosis, or major depression disorder with psychotic features and 299 healthy controls as part of the NORMENT study in Oslo, Norway. History of childhood trauma was obtained using the CTQ. Clinical diagnoses were assessed using the Structured Clinical Interview for DSM Disorders. Results: A significantly greater proportion of healthy controls (42.8%) had a positive MD score compared to patients (26.7%). When controlling for MD, the patient group still exhibited elevated reports of childhood trauma compared to controls (Cohen's d = 1.27), concordant with reports of childhood trauma being more frequently reported in a population of severe mental disorders. Conclusion: Elevated MD in the healthy control group could suggest an enhanced self-serving bias, potentially attenuated in the psychiatric group. Clinicians and researchers would benefit from including the MD component of CTQ when assessing retrospective information on childhood trauma to rule out potential effect of MD.

Polarized Ends of Human Macula Densa Cells: Ultrastructural Investigation and Morphofunctional Correlations.

PubMed

Cangiotti, Angela Maria; Lorenzi, Teresa; Zingaretti, Maria Cristina; Fabri, Mara; Morroni, Manrico

2018-05-01

The morphology of the kidney macula densa (MD) has extensively been investigated in animals, whereas human studies are scanty. We studied the fine structure of human MD cells focusing on their apical and basal ends and correlating structure and function. The MD region was examined by transmission electron microscopy in six renal biopsies from patients with kidney disease. Ultrastructural analysis of MD cells was performed on serial sections. MD cells show two polarized ends. The apical portion is characterized by a single, immotile cilium associated with microvilli; apically, cells are joined by adhering junctions. In the basal portion, the cytoplasm contains small, dense granules and numerous, irregular cytoplasmic projections extending to the adjacent extraglomerular mesangium. The projections often contain small, dense granules. A reticulated basement membrane around MD cells separates them from the extraglomerular mesangium. Although the fact that tissue specimens came from patients with kidney disease mandates extreme caution, ultrastructural examination confirmed that MD cells have sensory features due to the presence of the primary cilium, that they are connected by apical adhering junctions forming a barrier that separates the tubular flow from the interstitium, and that they present numerous basal interdigitations surrounded by a reticulated basement membrane. Conceivably, the latter two features are related to the functional activity of the MD. The small, dense granules in the basal cytoplasm and in cytoplasmic projections are likely related to the paracrine function of MD cells. Anat Rec, 301:922-931, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Levels of disability in major depression: findings from the Netherlands Mental Health Survey and Incidence Study (NEMESIS).

PubMed

Kruijshaar, M E; Hoeymans, N; Bijl, R V; Spijker, J; Essink-Bot, M L

2003-10-01

Information on the distribution of disability associated with major depression (MD) across different groups of patients is of interest to health policy and planning. We examined the associations of severity and type (a single or recurrent episode) of MD with disability in a Dutch general population sample. We used data from the first wave (1996) of the Netherlands Mental Health Survey and Incidence Study (NEMESIS). MD 'severity' and 'type' were diagnosed with the help of the Composite International Diagnostic Interview according to DSM-III-R criteria. SF-36 scores, days ill in bed and days absent from work were taken as indicators of disability. The differences in these variables were studied by means of variance and regression analysis. Recurrent MD was found not to be associated with more disability than single episode MD. Higher 'severity' classes were associated with more disability. However, the degree of disability between 'moderate' and 'severe' MD differed only very slightly. The difference in disability between non-depressed and mildly depressed individuals had a larger effect than between each successive pair of 'severity' classes. Three groups of MD can be distinguished based on the associated degree of disability: 'mild', 'moderate to severe' and 'severe with psychotic features'. In the future, these groups can be used to describe the distribution of disability in the depressed population. The marked difference between 'mild' MD and no MD suggests that 'mild' cases should be considered relevant.

Generation of physician-scientists manpower: a follow-up study of the first 294 graduates of the Harvard-MIT Program of Health Sciences and Technology.

PubMed

Abelmann, W H; Nave, B D; Wilkerson, L

1997-06-01

The MD program of the Harvard-MIT Division of Health Sciences and Technology was founded in 1970. One of its goals was the application of the academic resources of the two universities to the education of leaders in academic medicine and biomedical sciences. The first MD class was admitted in 1971. Prerequisites for admission are a strong background in quantitative sciences and demonstrated interest in research. Research and a thesis are obligatory. Enrollment in a PhD program is elective. Questionnaires were sent to 293 alumni who graduated from the MD program between 1975 and 1988, followed up by letters and telephone calls. By 1988, 296 students had graduated, 207 with an MD only, 89 with MD-PhD degrees. Follow-up by questionnaires of 293 living graduates (92%), plus indirect data on 11 others, revealed that 212 (75%) held faculty appointments in 64 medical schools. Overall, 73.5% of respondents were engaged in research: 68% of MDs and 86% of MD-PhDs. One hundred and four (38%) respondents spent more than 50% of their time on research: 54 (29%) of MDs and 50 (60%) of MD-PhDs. Seventy-five percent of respondents were active in teaching. Our experience indicates that both an MD-PhD program and a research-oriented MD program are effective in producing physician-scientists and leaders in academic medicine.

Musician's dystonia is highly task specific: no strong evidence for everyday fine motor deficits in patients.

PubMed

Hofmann, Aurélie; Grossbach, Michael; Baur, Volker; Hermsdörfer, Joachim; Altenmüller, Eckart

2015-03-01

1) To examine the fine motor skills used everyday by patients suffering from musician's dystonia (MD) in the upper limb in order to verify whether MD is task-specific; and 2) to compare the affected and non-affected hands of MD musicians vs healthy musicians in performance of these tasks in order to clarify whether dystonic symptoms can be found in the non-affected side of MD patients. MD is typically considered to be focal and task specific, but patients often report impairment in everyday life activities. Furthermore, in the course of MD, about 15% of patients complain of dystonic symptoms in other parts of the body. Twenty-seven musicians affected by MD and 27 healthy musicians were studied using 1) the Motor Performance Test Series, 2) a kinematic analysis of handwriting, and 3) an assessment of the grip force regulation while lifting and moving a manipulandum. Patients performed most fine motor tasks without any evidence of a deficit. Exclusively in the handwriting tasks (2), they exhibited fewer frequencies of the written trace and a prolonged overall writing time. MD is highly task specific and does not strongly affect other motor skills. The subtle deficits in handwriting may be explained as a consequence of a general psychological disposition rather than as compensatory mechanisms to avoid the appearance of dystonic symptoms. Furthermore, we did not find signs of multifocal motor deficits in the unaffected hands of MD patients.

A SMAD4 mutation indicative of juvenile polyposis syndrome in a family previously diagnosed with Menetrier's disease.

PubMed

Burmester, James K; Bell, Lauren N; Cross, Deanna; Meyer, Patrick; Yale, Steven H

2016-10-01

Menetrier's disease (MD) is a rare disease with unknown aetiology, characterized by hypertrophic folds within the fundus and body of the stomach. We investigated mutations of the candidate genes SMAD4, BMPR1A, TGF-α, and PDX1 within a family with MD. A large 4-generation family with MD was identified. This family had 5 cases of MD, 1 case of MD and juvenile polyposis syndrome (JPS) and 3 cases of JPS. Participants provided saliva for DNA extraction and completed a health questionnaire designed to assess conditions that may be found in patients with MD. Following pedigree analysis, we sequenced the coding regions of the SMAD4 and BMPR1A genes and the regulatory regions of the TGF-α and PDX1 genes in affected and non-affected family members. No mutations were identified in the sequenced regions of BMPR1A, TGF-α, or PDX1. A dominant 1244_1247delACAG mutation of SMAD4 was identified in each of the subjects with JPS as well as in each of the subjects with MD. Although this mutation segregated with disease, there were also unaffected/undiagnosed carriers. The 1244_1247delACAG mutation of SMAD4 is the cause of JPS and the likely cause of MD in a large family initially diagnosed with MD. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

LifeBridge new publication: Md.MD. Listing of 1,200 physicians a major part of consumer-type magazine.

PubMed

Botvin, Judith D

2004-01-01

LifeBridge Health, Baltimore, created a directory of its physicians, which developed into a 100-page consumer magazine titled Md.MD A Directory of the Region's Finest Physicians. Written and designed in-house, the premier edition paid for itself, thanks to publishing partner, Alter Communications. The premier edition was mailed to 50,000 Baltimore area homes last September.

Atropine Pharmacokinetics are Affected by Moderate Hemorrhage and Hypothyroidism

DTIC Science & Technology

1989-12-01

Moderate Hemorrhage and Hypothyroidism 12. PERSONAL AUTHOR(S) R.C. Smallridge, B. Chernow, S. Teich, C. Kinzer, C. Umstott, G. Geelhoed, _ Ppmnl i n 13a...moderate hemorrhage and hypothyroidism ROBERT C. SMALLRIDGE, MD: BART CHERNOW, MD: STEVEN TEICH, MD, CAROL KINZER: CAROLYN UMSTOTT: GLEN GEELHOED. MD...under two experimental conditions, moderate hem- sweating) are known (1-5). orrhage and hypothyroidism , to determine whether im A number of situations

CALS Test Network Handbook

DTIC Science & Technology

1993-03-01

Ltd Gillette Company Dorset, England Boston MA Foreign Broadcast Information Set. Giordano Associates Inc Frederick MD Long Branch NJ Formtek Inc...Associates Orem UT College Park MD InfoDesign Corp Johns Hopkins University Toronto, Ontario Laurel MD Information Spectrum Inc Joint Committee on Printing...Inc Washington DC Bel Air MD Navy Naval Research Laboratory OutSource Inc Washington DC Los Angeles CA 22 i +’ . S.. . -- -,•w• -- w,,Wmwmm mm -- m mmm

75 FR 38017 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-9-10 Series Airplanes, DC-9-30...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-01

... Airworthiness Directives; McDonnell Douglas Corporation Model DC- 9-10 Series Airplanes, DC-9-30 Series Airplanes, DC-9-81 (MD-81) Airplanes, DC-9-82 (MD-82) Airplanes, DC-9-83 (MD-83) Airplanes, DC-9- 87 (MD-87... Building Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590, between 9 a.m. and...

75 FR 80744 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-9-81 (MD-81), DC-9-82 (MD-82...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-23

...: We propose to adopt a new airworthiness directive (AD) for all Model DC-9-81 (MD-81), DC-9-82 (MD-82... inspections for cracking of the left and right upper center skin panels of the horizontal stabilizer, and..., West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590. Hand...

Muscle dysmorphia: could it be classified as an addiction to body image?

PubMed

Foster, Andrew C; Shorter, Gillian W; Griffiths, Mark D

2015-03-01

Muscle dysmorphia (MD) describes a condition characterised by a misconstrued body image in which individuals who interpret their body size as both small or weak even though they may look normal or highly muscular.MD has been conceptualized as a type of body dysmorphic disorder, an eating disorder, and obsessive–compulsive disorder symptomatology. METHOD AND AIM: Through a review of the most salient literature on MD, this paper proposes an alternative classification of MD--the ‘Addiction to Body Image’ (ABI) model--using Griffiths (2005)addiction components model as the framework in which to define MD as an addiction. It is argued the addictive activity in MD is the maintaining of body image via a number of different activities such as bodybuilding, exercise,eating certain foods, taking specific drugs (e.g., anabolic steroids), shopping for certain foods, food supplements,and the use or purchase of physical exercise accessories). In the ABI model, the perception of the positive effects on the self-body image is accounted for as a critical aspect of the MD condition (rather than addiction to exercise or certain types of eating disorder). Based on empirical evidence to date, it is proposed that MD could be re-classified as an addiction due to the individual continuing to engage in maintenance behaviours that may cause long-term harm.

Perceived parenting and risk for major depression in Chinese women

PubMed Central

Gao, J.; Li, Y.; Cai, Y.; Chen, J.; Shen, Y.; Ni, S.; Wei, Y.; Qiu, Y.; Zhu, X.; Liu, Y.; Lu, C.; Chen, C.; Niu, Q.; Tang, C.; Yang, Y.; Wang, Q.; Cui, W.; Xia, J.; Liu, T.; Zhang, J.; Zhao, B.; Guo, Z.; Pan, J.; Chen, H.; Luo, Y.; Sun, L.; Xiao, X.; Chen, Q.; Zhao, X.; He, F.; Lv, L.; Guo, L.; Liu, L.; Li, H.; Shi, S.; Flint, J.; Kendler, K. S.; Tao, M.

2012-01-01

Background In Western countries, a history of major depression (MD) is associated with reports of received parenting that is low in warmth and caring and high in control and authoritarianism. Does a similar pattern exist in women in China? Method Received parenting was assessed by a shortened version of the Parental Bonding Instrument (PBI) in two groups of Han Chinese women: 1970 clinically ascertained cases with recurrent MD and 2597 matched controls. MD was assessed at personal interview. Results Factor analysis of the PBI revealed three factors for both mothers and fathers: warmth, protectiveness, and authoritarianism. Lower warmth and protectiveness and higher authoritarianism from both mother and father were significantly associated with risk for recurrent MD. Parental warmth was positively correlated with parental protectiveness and negatively correlated with parental authoritarianism. When examined together, paternal warmth was more strongly associated with lowered risk for MD than maternal warmth. Furthermore, paternal protectiveness was negatively and maternal protectiveness positively associated with risk for MD. Conclusions Although the structure of received parenting is very similar in China and Western countries, the association with MD is not. High parental protectiveness is generally pathogenic in Western countries but protective in China, especially when received from the father. Our results suggest that cultural factors impact on patterns of parenting and their association with MD. PMID:21943491

Development of motion-defined figure-ground segregation in preschool and older children, using a letter-identification task.

PubMed

Giaschi, D; Regan, D

1997-09-01

Three-month-old infants can discriminate motion-defined (MD) form, but we do not know the age at which this ability reaches adult levels. Previous psychophysical evidence suggests that different neural mechanisms are involved in the processing of luminance-defined (LD) and MD spatial form in adults. This difference may be reflected in the development of LD versus MD form identification in children. We measured speed threshold for identifying MD letters, letter-chart (i.e, Snellen) acuity for high-contrast LD letters and single-letter acuity for high- and low-contrast LD letters. Forty-seven children between 3 and 12 years of age and 20 adult subjects were tested. Development to the adult level was observed as follows: low-contrast single-letter acuity before 3 years; high-contrast single-letter acuity by 5 to 6 years; the ability to identify MD letters by 7 to 8 years; letter-chart acuity by 9 to 10 years. MD form identification continues to mature in preschool children. LD form identification also matures in this age group but with a different time course. MD letters are not equivalent to low-contrast letters developmentally. Our findings provide further support for the hypothesis that the spatial aspects of MD and LD form are processed separately to some extent.

Review of the fundamental theories behind small angle X-ray scattering, molecular dynamics simulations, and relevant integrated application.

PubMed

Boldon, Lauren; Laliberte, Fallon; Liu, Li

2015-01-01

In this paper, the fundamental concepts and equations necessary for performing small angle X-ray scattering (SAXS) experiments, molecular dynamics (MD) simulations, and MD-SAXS analyses were reviewed. Furthermore, several key biological and non-biological applications for SAXS, MD, and MD-SAXS are presented in this review; however, this article does not cover all possible applications. SAXS is an experimental technique used for the analysis of a wide variety of biological and non-biological structures. SAXS utilizes spherical averaging to produce one- or two-dimensional intensity profiles, from which structural data may be extracted. MD simulation is a computer simulation technique that is used to model complex biological and non-biological systems at the atomic level. MD simulations apply classical Newtonian mechanics' equations of motion to perform force calculations and to predict the theoretical physical properties of the system. This review presents several applications that highlight the ability of both SAXS and MD to study protein folding and function in addition to non-biological applications, such as the study of mechanical, electrical, and structural properties of non-biological nanoparticles. Lastly, the potential benefits of combining SAXS and MD simulations for the study of both biological and non-biological systems are demonstrated through the presentation of several examples that combine the two techniques.

Influence of family history of major depression, bipolar disorder, and suicide on clinical features in patients with major depression and bipolar disorder.

PubMed

Serretti, Alessandro; Chiesa, Alberto; Calati, Raffaella; Linotte, Sylvie; Sentissi, Othman; Papageorgiou, Konstantinos; Kasper, Siegfried; Zohar, Joseph; De Ronchi, Diana; Mendlewicz, Julien; Amital, Daniela; Montgomery, Stuart; Souery, Daniel

2013-03-01

The extent to which a family history of mood disorders and suicide could impact on clinical features of patients suffering from major depression (MD) and bipolar disorder (BD) has received relatively little attention so far. The aim of the present work is, therefore, to assess the clinical implications of the presence of at least one first- and/or second-degree relative with a history of MD, BD and suicide in a large sample of patients with MD or BD. One thousand one hundred and fifty-seven subjects with MD and 686 subjects with BD were recruited within the context of two large projects. The impact of a family history of MD, BD, and suicide-considered both separately and together-on clinical and socio-demographic variables was investigated. A family history of MD, BD, and suicide was more common in BD patients than in MD patients. A positive family history of mood disorders and/or suicide as well as a positive family history of MD and BD separately considered, but not a positive history of suicide alone, were significantly associated with a comorbidity with several anxiety disorders and inversely associated with age of onset. The clinical implications as well as the limitations of our findings are discussed.

Mathematical learning disorder in school-age children with attention-deficit hyperactivity disorder.

PubMed

Capano, Lucia; Minden, Debbie; Chen, Shirley X; Schacher, Russell J; Ickowicz, Abel

2008-06-01

To explore the prevalence of mathematics disorder (MD) relative to reading disorders (RD) in school-age children with attention-deficit hyperactivity disorder (ADHD) and examine the effects of age, sex, cooccurring conduct disorder (CD), and ADHD subtype on this comorbidity. Participants were school-age children (n = 476) with confirmed DSM-IV diagnosis of ADHD. The assessment included semistructured parent and teacher interviews and standardized measures of intelligence, academic attainment, and language abilities. Based on the presence or absence of concurrent learning disorders, we compared the emerging 4 groups: ADHD-only, ADHD + MD, ADHD + RD, and ADHD + MD + RD. Overall prevalence of comorbid ADHD + MD was 18.1%. Age, sex, ADHD subtypes, or comorbid CD did not affect the frequency of MD. Children with concurrent ADHD and either MD or RD attained lower IQ, language, and academic scores than those with ADHD alone. Children with ADHD + MD + RD were more seriously impaired and demonstrated distinct deficits in receptive and expressive language. MDs are relatively common in school-age children with ADHD and are frequently associated with RDs. Children with ADHD + MD + RD are more severely impaired. These deficits simply cannot be explained as consequences of ADHD and might have unique biological underpinnings, with implications for diagnostic classification and therapeutic interventions.

Cognitive Risk Factors for Specific Learning Disorder: Processing Speed, Temporal Processing, and Working Memory.

PubMed

Moll, Kristina; Göbel, Silke M; Gooch, Debbie; Landerl, Karin; Snowling, Margaret J

2016-01-01

High comorbidity rates between reading disorder (RD) and mathematics disorder (MD) indicate that, although the cognitive core deficits underlying these disorders are distinct, additional domain-general risk factors might be shared between the disorders. Three domain-general cognitive abilities were investigated in children with RD and MD: processing speed, temporal processing, and working memory. Since attention problems frequently co-occur with learning disorders, the study examined whether these three factors, which are known to be associated with attention problems, account for the comorbidity between these disorders. The sample comprised 99 primary school children in four groups: children with RD, children with MD, children with both disorders (RD+MD), and typically developing children (TD controls). Measures of processing speed, temporal processing, and memory were analyzed in a series of ANCOVAs including attention ratings as covariate. All three risk factors were associated with poor attention. After controlling for attention, associations with RD and MD differed: Although deficits in verbal memory were associated with both RD and MD, reduced processing speed was related to RD, but not MD; and the association with RD was restricted to processing speed for familiar nameable symbols. In contrast, impairments in temporal processing and visuospatial memory were associated with MD, but not RD. © Hammill Institute on Disabilities 2014.

Analysis of MD5 authentication in various routing protocols using simulation tools

NASA Astrophysics Data System (ADS)

Dinakaran, M.; Darshan, K. N.; Patel, Harsh

2017-11-01

Authentication being an important paradigm of security and Computer Networks require secure paths to make the flow of the data even more secure through some security protocols. So MD-5(Message Digest 5) helps in providing data integrity to the data being sent through it and authentication to the network devices. This paper gives a brief introduction to the MD-5, simulation of the networks by including MD-5 authentication using various routing protocols like OSPF, EIGRP and RIPv2. GNS3 is being used to simulate the scenarios. Analysis of the MD-5 authentication is done in the later sections of the paper.

An LQG Up-and Away Flight Control Design for the STOL F-15 Aircraft.

DTIC Science & Technology

1985-12-01

bmat ɜ,8) dimension dirmatC5,5),dirbmnat(5,9) character*3 Key, Keyl, datal, data2, data3, run characterti...write( *,*) now we’ll get the input matrix -b bmat (1,1) = xdl b rat ( 1,2) = xd2 bmat ( 1,3) = xd3 bmat <l,4) = xd4 bmat ( 1,5) = xd5 bmatc 1,6) = xd6 bmat ...1,7) = xd7 * bmat ( 1,8) = xd8 bmat (2,1) = mdl bmat (2,2) = md2 bmat (2,3) = md3 bmatc2,4) = md4 bmat ( 2,5) = md 5 bmatc2,6) = md6 bmat (2,7) =

Mitochondrial DNA in Residual Leukemia Cells in Cerebrospinal Fluid in Children with Acute Lymphoblastic Leukemia

PubMed Central

Egan, Kathryn; Kusao, Ian; Troelstrup, David; Agsalda, Melissa; Shiramizu, Bruce

2010-01-01

This feasibility study was designed to assess the ability to measure mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) cells that contributed to minimal disease/persistent or residual disease (MD/PRD) from children with acute lymphoblastic leukemia (ALL). Increase in mtDNA copies in cancer cells has been suggested to play a role in MD/PRD. CSF as well as blood specimens from 6 children were assayed for MD/PRD and mtDNA copy numbers by quantitative real-time polymerase chain reaction. Of 7 MD/PRD-positive specimens, 6 had increased mtDNA copy numbers; while 11 MD/PRD-negative specimens had no increase in mtDNA copy numbers, p < 0.003. This is the first proof-of-concept study to measure mtDNA copy numbers in MD/PRD-positive CSF specimens from children with ALL. Increase of mtDNA copy numbers in MD/PRD childhood ALL cells and its significance as a mechanism for recurrence requires further investigation. Keywords Minimal residual disease; Acute lymphoblastic leukemia; Central nervous system; Cerebrospinal fluid; Mitochondria PMID:21331151

Parallel cascade selection molecular dynamics (PaCS-MD) to generate conformational transition pathway

NASA Astrophysics Data System (ADS)

Harada, Ryuhei; Kitao, Akio

2013-07-01

Parallel Cascade Selection Molecular Dynamics (PaCS-MD) is proposed as a molecular simulation method to generate conformational transition pathway under the condition that a set of "reactant" and "product" structures is known a priori. In PaCS-MD, the cycle of short multiple independent molecular dynamics simulations and selection of the structures close to the product structure for the next cycle are repeated until the simulated structures move sufficiently close to the product. Folding of 10-residue mini-protein chignolin from the extended to native structures and open-close conformational transition of T4 lysozyme were investigated by PaCS-MD. In both cases, tens of cycles of 100-ps MD were sufficient to reach the product structures, indicating the efficient generation of conformational transition pathway in PaCS-MD with a series of conventional MD without additional external biases. Using the snapshots along the pathway as the initial coordinates, free energy landscapes were calculated by the combination with multiple independent umbrella samplings to statistically elucidate the conformational transition pathways.

Chronic neck pain and masticatory dysfunction.

PubMed

Catanzariti, Jean-François; Debuse, Thierry; Duquesnoy, Bernard

2005-12-01

Chronic nonspecific neck pain is a common problem in rheumatology and may resist conventional treatment. Pathophysiological links exist between the cervical spine and masticatory system. Occlusal disorders may cause neck pain and may respond to dental treatment. The estimated prevalence of occlusal disorders is about 45%, with half the cases being due to functional factors. Minor repeated masticatory dysfunction (MD) with craniocervical asymmetry is the most common clinical picture. The pain is usually located in the suboccipital region and refractory to conventional treatment. The time pattern may be suggestive, with nocturnal arousals or triggering by temporomandibular movements. MD should be strongly suspected in patients with at least two of the following: history of treated or untreated MD, unilateral temporomandibular joint pain and clicking, lateral deviation during mouth opening, and limitation of mouth opening (less than three fingerbreadths). Rheumatologists should consider MD among causes of neck pain, most notably in patients with abnormal craniocervical posture, signs linking the neck pain to mastication, and clinical manifestations of MD. Evidence suggesting that MD may cause neck pain has been published. However, studies are needed to determine whether treatment of MD can relieve neck pain.

76 FR 54408 - Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-01

...: Jerry Menikoff, M.D., J.D., OHRP, 1101 Wootton Parkway, Suite 200, Rockville, MD 20852. Comments... (OHRP), Department of Health and Human Services, 1101 Wootton Parkway, Suite 200, Rockville, MD 20852...

Infant Colic and Migraine: Is There a Connection?

MedlinePlus

... Spencer, MD Steven Karceski, MD Infant colic and migraine Is there a connection? Steven Karceski, MD Neal S. ... infant colic as an early life expression of migraine,” Dr. Gelfand and colleagues 1 studied a large ...

39. SAME VIEW AS MD6A38, ONLY WITH A HORIZONTAL ORIENTATION. ...

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

39. SAME VIEW AS MD-6A-38, ONLY WITH A HORIZONTAL ORIENTATION. - Baltimore & Ohio Railroad, Mount Clare Shops, South side of Pratt Street between Carey & Poppleton Streets, Baltimore, Independent City, MD

Acute Oral Toxicity (LD50) of 4-Nitrophenyl Monochloromethyl (Phenyl) Phosphinate (TA009) in Female Rats

DTIC Science & Technology

1984-10-01

Research Institute Aberden Proving Ground MD 21070 of Chemical Defense Aberdeen Proving Ground Edgcwood Arsenal MD 21010 US Army Research Office Commander...Aberdeen Proving Ground , MD 21010-5012 PROJECT: 35162772A875 Medical Defense Against Chemical Agents WU 304 Toxicity Testing of Phosphinate Compounds APC...Institute of Chemical Defense, Aberdeen Proving Ground , MD 21010 on 23 June 1982. The test chemical was stored at refrigeration temperature (as

Association of spirochetal infection with Morgellons disease.

PubMed

Middelveen, Marianne J; Burugu, Divya; Poruri, Akhila; Burke, Jennie; Mayne, Peter J; Sapi, Eva; Kahn, Douglas G; Stricker, Raphael B

2013-01-01

Morgellons disease (MD) is an emerging multisystem illness characterized by skin lesions with unusual filaments embedded in or projecting from epithelial tissue. Filament formation results from abnormal keratin and collagen expression by epithelial-based keratinocytes and fibroblasts. Recent research comparing MD to bovine digital dermatitis, an animal infectious disease with similar skin features, provided clues that spirochetal infection could play an important role in the human disease as it does in the animal illness. Based on histological staining, immunofluorescent staining, electron microscopic imaging and polymerase chain reaction, we report the detection of Borrelia spirochetes in dermatological tissue of  four randomly-selected MD patients. The association of MD with spirochetal infection provides evidence that this infection may be a significant factor in the illness and refutes claims that MD lesions are self-inflicted and that people suffering from this disorder are delusional. Molecular characterization of the Borrelia spirochetes found in MD patients is warranted.

Association of spirochetal infection with Morgellons disease

PubMed Central

Stricker, Raphael B

2013-01-01

Morgellons disease (MD) is an emerging multisystem illness characterized by skin lesions with unusual filaments embedded in or projecting from epithelial tissue. Filament formation results from abnormal keratin and collagen expression by epithelial-based keratinocytes and fibroblasts. Recent research comparing MD to bovine digital dermatitis, an animal infectious disease with similar skin features, provided clues that spirochetal infection could play an important role in the human disease as it does in the animal illness. Based on histological staining, immunofluorescent staining, electron microscopic imaging and polymerase chain reaction, we report the detection of Borrelia spirochetes in dermatological tissue of  four randomly-selected MD patients. The association of MD with spirochetal infection provides evidence that this infection may be a significant factor in the illness and refutes claims that MD lesions are self-inflicted and that people suffering from this disorder are delusional. Molecular characterization of the Borrelia spirochetes found in MD patients is warranted. PMID:24715950

A novel energy conversion based method for velocity correction in molecular dynamics simulations

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

Jin, Hanhui; Collaborative Innovation Center of Advanced Aero-Engine, Hangzhou 310027; Liu, Ningning

2017-05-01

Molecular dynamics (MD) simulation has become an important tool for studying micro- or nano-scale dynamics and the statistical properties of fluids and solids. In MD simulations, there are mainly two approaches: equilibrium and non-equilibrium molecular dynamics (EMD and NEMD). In this paper, a new energy conversion based correction (ECBC) method for MD is developed. Unlike the traditional systematic correction based on macroscopic parameters, the ECBC method is developed strictly based on the physical interaction processes between the pair of molecules or atoms. The developed ECBC method can apply to EMD and NEMD directly. While using MD with this method, themore » difference between the EMD and NEMD is eliminated, and no macroscopic parameters such as external imposed potentials or coefficients are needed. With this method, many limits of using MD are lifted. The application scope of MD is greatly extended.« less

Influence of the electron cyclotron resonance plasma confinement on reducing the bremsstrahlung production of an electron cyclotron resonance ion source with metal-dielectric structures.

PubMed

Schachter, L; Stiebing, K E; Dobrescu, S

2009-01-01

The influence of metal-dielectric (MD) layers (MD structures) inserted into the plasma chamber of an electron cyclotron resonance ion source (ECRIS) onto the production of electron bremsstrahlung radiation has been studied in a series of dedicated experiments at the 14 GHz ECRIS of the Institut für Kernphysik der Universität Frankfurt. The IKF-ECRIS was equipped with a MD liner, covering the inner walls of the plasma chamber, and a MD electrode, covering the plasma-facing side of the extraction electrode. On the basis of similar extracted currents of highly charged ions, significantly reduced yields of bremsstrahlung radiation for the "MD source" as compared to the standard (stainless steel) source have been measured and can be explained by the significantly better plasma confinement in a MD source as compared to an "all stainless steel" ECRIS.

Muscle Dysmorphia Symptomatology and Associated Psychological Features in Bodybuilders and Non-Bodybuilder Resistance Trainers: A Systematic Review and Meta-Analysis.

PubMed

Mitchell, Lachlan; Murray, Stuart B; Cobley, Stephen; Hackett, Daniel; Gifford, Janelle; Capling, Louise; O'Connor, Helen

2017-02-01

Muscle dysmorphia (MD) is associated with a self-perceived lack of size and muscularity, and is characterized by a preoccupation with and pursuit of a hyper-mesomorphic body. MD symptoms may hypothetically be more prevalent in bodybuilders (BBs) than in non-bodybuilder resistance trainers (NBBRTs). Our objective was to compare MD symptomatology in BBs versus NBBRTs and identify psychological and other characteristics associated with MD in these groups. We searched relevant databases from earliest record to February 2015 for studies examining MD symptoms in BBs and/or NBBRTs. Included studies needed to assess MD using a psychometrically validated assessment tool. Study quality was evaluated using an adapted version of the validated Downs and Black tool. We calculated between-group standardized mean difference (effect sizes [ESs]) and 95 % confidence intervals (CIs) for each MD subscale, and performed meta-analysis when five or more studies used the same MD tool. We also extracted data describing psychological or other characteristics associated with MD. Of the 2135 studies initially identified, 31 analyzing data on 5880 participants (BBs: n = 1895, NBBRTs: n = 3523, controls: n = 462) were eligible for inclusion, though study quality was generally poor-moderate (range 7-19/22). Most participants were male (90 %). Eight different MD assessment tools were used. Meta-analysis for five studies all using the Muscle Dysmorphia Inventory (MDI) revealed there was a medium to large pooled ES for greater MD symptomatology in BBs than in NBBRTs on all MDI subscales (ES 0.53-1.12; p ≤ 0.01). Competitive BBs scored higher than non-competitive BBs (ES 1.21, 95 % CI 0.82-1.60; p < 0.001). MD symptoms were associated with anxiety (r 0.32-0.42; p ≤ 0.01), social physique anxiety (r 0.26-0.75; p < 0.01), depression (r 0.23-0.53; p ≤ 0.01), neuroticism (r 0.38; p < 0.001), and perfectionism (r 0.35; p < 0.05) and were inversely associated with self-concept (r -0.32 to -0.36; p < 0.01) and self-esteem (r -0.42 to -0.47; p < 0.01). MD symptomatology was greater in BBs than in NBBRTs. Anxiety and social physique anxiety, depression, neuroticism, and perfectionism were positively associated with MD, while self-concept and self-esteem were negatively associated. It remains unclear whether these characteristics are exacerbated by bodybuilding, or whether individuals with these characteristics are attracted to the bodybuilding context.

Causal Evidence from Humans for the Role of Mediodorsal Nucleus of the Thalamus in Working Memory.

PubMed

Peräkylä, Jari; Sun, Lihua; Lehtimäki, Kai; Peltola, Jukka; Öhman, Juha; Möttönen, Timo; Ogawa, Keith H; Hartikainen, Kaisa M

2017-12-01

The mediodorsal nucleus of the thalamus (MD), with its extensive connections to the lateral pFC, has been implicated in human working memory and executive functions. However, this understanding is based solely on indirect evidence from human lesion and imaging studies and animal studies. Direct, causal evidence from humans is missing. To obtain direct evidence for MD's role in humans, we studied patients treated with deep brain stimulation (DBS) for refractory epilepsy. This treatment is thought to prevent the generalization of a seizure by disrupting the functioning of the patient's anterior nuclei of the thalamus (ANT) with high-frequency electric stimulation. This structure is located superior and anterior to MD, and when the DBS lead is implanted in ANT, tip contacts of the lead typically penetrate through ANT into the adjoining MD. To study the role of MD in human executive functions and working memory, we periodically disrupted and recovered MD's function with high-frequency electric stimulation using DBS contacts reaching MD while participants performed a cognitive task engaging several aspects of executive functions. We hypothesized that the efficacy of executive functions, specifically working memory, is impaired when the functioning of MD is perturbed by high-frequency stimulation. Eight participants treated with ANT-DBS for refractory epilepsy performed a computer-based test of executive functions while DBS was repeatedly switched ON and OFF at MD and at the control location (ANT). In comparison to stimulation of the control location, when MD was stimulated, participants committed 2.26 times more errors in general (total errors; OR = 2.26, 95% CI [1.69, 3.01]) and 2.86 times more working memory-related errors specifically (incorrect button presses; OR = 2.88, CI [1.95, 4.24]). Similarly, participants committed 1.81 more errors in general ( OR = 1.81, CI [1.45, 2.24]) and 2.08 times more working memory-related errors ( OR = 2.08, CI [1.57, 2.75]) in comparison to no stimulation condition. "Total errors" is a composite score consisting of basic error types and was mostly driven by working memory-related errors. The facts that MD and a control location, ANT, are only few millimeters away from each other and that their stimulation produces very different results highlight the location-specific effect of DBS rather than regionally unspecific general effect. In conclusion, disrupting and recovering MD's function with high-frequency electric stimulation modulated participants' online working memory performance providing causal, in vivo evidence from humans for the role of MD in human working memory.

Cross-sectional-derived determinants of satisfaction with physician-scientist training among Canadian MD/PhD graduates.

PubMed

Twa, David D W; Skinnider, Michael A; Squair, Jordan W; Lukac, Christine D

2017-01-01

Although MD/PhD programs require considerable commitment on behalf of students and learning institutions, they serve as an integral means of training future physician-scientists; individuals who engage in translational medicine. As attrition from these programs has longstanding effects on the community of translational medicine and comes at substantial cost to MD/PhD programs, we aimed to identify determinants that were associated with satisfaction among MD/PhD graduates, a feature that might inform on limiting program attrition. Anonymized data from a national survey of 139 Canadian MD/PhD alumni was analyzed. Factor analysis was conducted to evaluate the reliability of three questions that measured satisfaction and logistic regression was used to assess the association of outcomes with 17 independent determinants. Eighty-one percent of graduates were satisfied with MD/PhD training. Factor analysis confirmed the reliability of the questions measuring satisfaction. Determinants of self-reported satisfaction with physician-scientist training included co-authorship of more than six manuscripts during MD/PhD training. Additionally, protected research time at the place of current appointment was strongly associated with agreement that MD/PhD training had helped career progression. Demographic variables were not associated with any satisfaction indicator. Taken together, the majority of Canadian MD/PhD graduates are satisfied with their physician-scientist training. Project collaboration leading to co-authorships and protected research time were strongly associated with training satisfaction among graduates. If the value of collaboration can be realized among current and future physician-scientist trainees who are dissatisfied with their training, this might ultimately reduce program attrition.

Image fusion in craniofacial virtual reality modeling based on CT and 3dMD photogrammetry.

PubMed

Xin, Pengfei; Yu, Hongbo; Cheng, Huanchong; Shen, Shunyao; Shen, Steve G F

2013-09-01

The aim of this study was to demonstrate the feasibility of building a craniofacial virtual reality model by image fusion of 3-dimensional (3D) CT models and 3 dMD stereophotogrammetric facial surface. A CT scan and stereophotography were performed. The 3D CT models were reconstructed by Materialise Mimics software, and the stereophotogrammetric facial surface was reconstructed by 3 dMD patient software. All 3D CT models were exported as Stereo Lithography file format, and the 3 dMD model was exported as Virtual Reality Modeling Language file format. Image registration and fusion were performed in Mimics software. Genetic algorithm was used for precise image fusion alignment with minimum error. The 3D CT models and the 3 dMD stereophotogrammetric facial surface were finally merged into a single file and displayed using Deep Exploration software. Errors between the CT soft tissue model and 3 dMD facial surface were also analyzed. Virtual model based on CT-3 dMD image fusion clearly showed the photorealistic face and bone structures. Image registration errors in virtual face are mainly located in bilateral cheeks and eyeballs, and the errors are more than 1.5 mm. However, the image fusion of whole point cloud sets of CT and 3 dMD is acceptable with a minimum error that is less than 1 mm. The ease of use and high reliability of CT-3 dMD image fusion allows the 3D virtual head to be an accurate, realistic, and widespread tool, and has a great benefit to virtual face model.

Can Vestibular-Evoked Myogenic Potentials Help Differentiate Ménière Disease from Vestibular Migraine?

PubMed Central

Zuniga, M. Geraldine; Janky, Kristen L.; Schubert, Michael C.; Carey, John P.

2013-01-01

Objectives To characterize both cervical and ocular vestibular-evoked myogenic potential (cVEMP, oVEMP) responses to air-conducted sound (ACS) and midline taps in Ménière disease (MD), vestibular migraine (VM), and controls, as well as to determine if cVEMP or oVEMP responses can differentiate MD from VM. Study Design Prospective cohort study. Setting Tertiary referral center. Subjects and Methods Unilateral definite MD patients (n = 20), VM patients (n = 21) by modified Neuhauser criteria, and age-matched controls (n = 28). cVEMP testing used ACS (clicks), and oVEMP testing used ACS (clicks and 500-Hz tone bursts) and midline tap stimuli (reflex hammer and Mini-Shaker). Outcome parameters were cVEMP peak-to-peak amplitudes and oVEMP n10 amplitudes. Results Relative to controls, MD and VM groups both showed reduced click-evoked cVEMP (P < .001) and oVEMP (P < .001) amplitudes. Only the MD group showed reduction in tone-evoked amplitudes for oVEMP. Tone-evoked oVEMPs differentiated MD from controls (P = .001) and from VM (P = .007). The oVEMPs in response to the reflex hammer and Mini-Shaker midline taps showed no differences between groups (P > .210). Conclusions Using these techniques, VM and MD behaved similarly on most of the VEMP test battery. A link in their pathophysiology may be responsible for these responses. The data suggest a difference in 500-Hz tone burst–evoked oVEMP responses between MD and MV as a group. However, no VEMP test that was investigated segregated individuals with MD from those with VM. PMID:22267492

Properties of pattern standard deviation in open-angle glaucoma patients with hemi-optic neuropathy and bi-optic neuropathy.

PubMed

Heo, Dong Won; Kim, Kyoung Nam; Lee, Min Woo; Lee, Sung Bok; Kim, Chang-Sik

2017-01-01

To evaluate the properties of pattern standard deviation (PSD) according to localization of the glaucomatous optic neuropathy. We enrolled 242 eyes of 242 patients with primary open-angle glaucoma, with a best-corrected visual acuity ≥ 20/25, and no media opacity. Patients were examined via dilated fundus photography, spectral-domain optical coherence tomography, and Humphrey visual field examination, and divided into those with hemi-optic neuropathy (superior or inferior) and bi-optic neuropathy (both superior and inferior). We assessed the relationship between mean deviation (MD) and PSD. Using broken stick regression analysis, the tipping point was identified, i.e., the point at which MD became significantly associated with a paradoxical reversal of PSD. In 91 patients with hemi-optic neuropathy, PSD showed a strong correlation with MD (r = -0.973, β = -0.965, p < 0.001). The difference between MD and PSD ("-MD-PSD") was constant (mean, -0.32 dB; 95% confidence interval, -2.48~1.84 dB) regardless of visual field defect severity. However, in 151 patients with bi-optic neuropathy, a negative correlation was evident between "-MD-PSD" and MD (r2 = 0.907, p < 0.001). Overall, the MD tipping point was -14.0 dB, which was close to approximately 50% damage of the entire visual field (p < 0.001). Although a false decrease of PSD usually begins at approximately 50% visual field damage, in patients with hemi-optic neuropathy, the PSD shows no paradoxical decrease and shows a linear correlation with MD.

Frequency of a natural truncated allele of MdMLO19 in the germplasm of Malus domestica.

PubMed

Pessina, Stefano; Palmieri, Luisa; Bianco, Luca; Gassmann, Jennifer; van de Weg, Eric; Visser, Richard G F; Magnago, Pierluigi; Schouten, Henk J; Bai, Yuling; Riccardo Velasco, R; Malnoy, Mickael

2017-01-01

Podosphaera leucotricha is the causal agent of powdery mildew (PM) in apple. To reduce the amount of fungicides required to control this pathogen, the development of resistant apple cultivars should become a priority. Resistance to PM was achieved in various crops by knocking out specific members of the MLO gene family that are responsible for PM susceptibility (S-genes). In apple, the knockdown of MdMLO19 resulted in PM resistance. However, since gene silencing technologies such as RNAi are perceived unfavorably in Europe, a different approach that exploits this type of resistance is needed. This work evaluates the presence of non-functional naturally occurring alleles of MdMLO19 in apple germplasm. The screening of the re-sequencing data of 63 apple individuals led to the identification of 627 single nucleotide polymorphisms (SNPs) in five MLO genes ( MdMLO5, MdMLO7, MdMLO11, MdMLO18 , and MdMLO19 ), 127 of which were located in exons. The T-1201 insertion of a single nucleotide in MdMLO19 caused the formation of an early stop codon, resulting in a truncated protein lacking 185 amino acids, including the calmodulin-binding domain. The presence of the insertion was evaluated in 115 individuals. It was heterozygous in 64 and homozygous in 25. Twelve of the 25 individuals carrying the insertion in homozygosity were susceptible to PM. After barley, pea, cucumber, and tomato, apple would be the fifth species for which a natural non-functional mlo allele has been found.

Factors that influence standard automated perimetry test results in glaucoma: test reliability, technician experience, time of day, and season.

PubMed

Junoy Montolio, Francisco G; Wesselink, Christiaan; Gordijn, Marijke; Jansonius, Nomdo M

2012-10-09

To determine the influence of several factors on standard automated perimetry test results in glaucoma. Longitudinal Humphrey field analyzer 30-2 Swedish interactive threshold algorithm data from 160 eyes of 160 glaucoma patients were used. The influence of technician experience, time of day, and season on the mean deviation (MD) was determined by performing linear regression analysis of MD against time on a series of visual fields and subsequently performing a multiple linear regression analysis with the MD residuals as dependent variable and the factors mentioned above as independent variables. Analyses were performed with and without adjustment for the test reliability (fixation losses and false-positive and false-negative answers) and with and without stratification according to disease stage (baseline MD). Mean follow-up was 9.4 years, with on average 10.8 tests per patient. Technician experience, time of day, and season were associated with the MD. Approximately 0.2 dB lower MD values were found for inexperienced technicians (P < 0.001), tests performed after lunch (P < 0.001), and tests performed in the summer or autumn (P < 0.001). The effects of time of day and season appeared to depend on disease stage. Independent of these effects, the percentage of false-positive answers strongly influenced the MD with a 1 dB increase in MD per 10% increase in false-positive answers. Technician experience, time of day, season, and the percentage of false-positive answers have a significant influence on the MD of standard automated perimetry.

Portable Body Temperature Conditioner

DTIC Science & Technology

2012-10-01

TITLE: Portable Body Temperature Conditioner PRINCIPAL INVESTIGATOR...Body Temperature Conditioner 5b. GRANT NUMBER W81XWH-11-1-0792 5c... Conditioner Principal Investigator: Timothy D. Browder, MD Co-Investigator: Deborah Kuhls, MD Co-Investigator: John Fildes, MD Table of Contents

Interior view, general view in covered causeway (MD1109W) near ward ...

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

Interior view, general view in covered causeway (MD-1109-W) near ward 114, looking from the northwest - National Park Seminary, Music Hall, Linden Lane at western edge of campus, Silver Spring, Montgomery County, MD

Effects of two-temperature model on cascade evolution in Ni and NiFe

DOE PAGES

Samolyuk, German D.; Xue, Haizhou; Bei, Hongbin; ...

2016-07-05

We perform molecular dynamics simulations of Ni ion cascades in Ni and equiatomic NiFe under the following conditions: (a) classical molecular dynamics (MD) simulations without consideration of electronic energy loss, (b) classical MD simulations with the electronic stopping included, and (c) using the coupled two-temperature MD (2T-MD) model that incorporates both the electronic stopping and the electron-phonon interactions. Our results indicate that the electronic effects are more profound in the higher-energy cascades, and that the 2T-MD model results in a smaller amount of surviving damage and smaller defect clusters, while less damage is produced in NiFe than in Ni.

M1A2 Adjunct Analysis (POSNOV Volume)

DTIC Science & Technology

1989-12-01

MD 20814-2797 Director 2 U.S. Army Materiel Systems Analysis Activity ATTN: AMXSY-CS, AMXSY-GA Aberden Proving Grounds , MD 21005-5071 U.S. Army...Leonard Wood, MO Commander U.S. Army Ordnance Center & School ATTN: ATSL-CD-CS Aberdeen Proving Ground , MD 21005 Commander 2 U.S. Army Soldier Support...NJ Commander U.S. Army Test and Evaluation Command ATrN: AMSTE-CM-R Aberdeen Proving Ground , MD 21005 Commander U.S. Army Tank Automotive Command

Dipole Models for UXO Discrimination at Live Sites - Pole Mountain

DTIC Science & Technology

2012-06-01

48 ESTCP MR-201159 Pole Mountain Demonstration Report viii April 2012 Acronyms API Application Programming...working on transitioning our inversion algorithms to an API that will be generally accessible. 8 3. PERFORMANCE OBJECTIVES The performance...2098 35 0 0 Frag (light) 6 MD PM-2098 35 0 0 Frag (light) 4 MD PM-2098 35 0 0 Frag (light) 3.5 MD PM-1354 8.5 0 0 Frag (medium) 5 MD PM- 1104 3 15

Muscle dysmorphia: Could it be classified as an addiction to body image?

PubMed Central

FOSTER, ANDREW C.; SHORTER, GILLIAN W.

2015-01-01

Background Muscle dysmorphia (MD) describes a condition characterised by a misconstrued body image in which individuals who interpret their body size as both small or weak even though they may look normal or highly muscular. MD has been conceptualized as a type of body dysmorphic disorder, an eating disorder, and obsessive–compulsive disorder symptomatology. Method and aim Through a review of the most salient literature on MD, this paper proposes an alternative classification of MD – the ‘Addiction to Body Image’ (ABI) model – using Griffiths (2005) addiction components model as the framework in which to define MD as an addiction. Results It is argued the addictive activity in MD is the maintaining of body image via a number of different activities such as bodybuilding, exercise, eating certain foods, taking specific drugs (e.g., anabolic steroids), shopping for certain foods, food supplements, and the use or purchase of physical exercise accessories). In the ABI model, the perception of the positive effects on the self-body image is accounted for as a critical aspect of the MD condition (rather than addiction to exercise or certain types of eating disorder). Conclusions Based on empirical evidence to date, it is proposed that MD could be re-classified as an addiction due to the individual continuing to engage in maintenance behaviours that may cause long-term harm. PMID:25592218

Review of the fundamental theories behind small angle X-ray scattering, molecular dynamics simulations, and relevant integrated application

PubMed Central

Boldon, Lauren; Laliberte, Fallon; Liu, Li

2015-01-01

In this paper, the fundamental concepts and equations necessary for performing small angle X-ray scattering (SAXS) experiments, molecular dynamics (MD) simulations, and MD-SAXS analyses were reviewed. Furthermore, several key biological and non-biological applications for SAXS, MD, and MD-SAXS are presented in this review; however, this article does not cover all possible applications. SAXS is an experimental technique used for the analysis of a wide variety of biological and non-biological structures. SAXS utilizes spherical averaging to produce one- or two-dimensional intensity profiles, from which structural data may be extracted. MD simulation is a computer simulation technique that is used to model complex biological and non-biological systems at the atomic level. MD simulations apply classical Newtonian mechanics’ equations of motion to perform force calculations and to predict the theoretical physical properties of the system. This review presents several applications that highlight the ability of both SAXS and MD to study protein folding and function in addition to non-biological applications, such as the study of mechanical, electrical, and structural properties of non-biological nanoparticles. Lastly, the potential benefits of combining SAXS and MD simulations for the study of both biological and non-biological systems are demonstrated through the presentation of several examples that combine the two techniques. PMID:25721341

Science in the clinic: a qualitative study of the positioning of MD-PhDs in the everyday clinical setting.

PubMed

Andreassen, Pernille; Christensen, Mette Krogh

2018-05-25

MD-PhDs have been hailed as significant to the advancement of medicine and health care. Yet when it comes to which positions MD-PhDs should be holding in the clinic and the academic world, there seems to be no real consensus. This article examines the ways in which a PhD-degree may contribute to medical doctors' professional practice in the clinic and discusses the positioning of MD-PhDs in the clinic. The study is explorative and qualitative, based on interviews with MD-PhDs, their physician colleagues without a PhD-degree, and their leaders. Positioning theory was applied as the analytical framework for data analysis. We found two opposing positions cutting across the groups of informants with one side critiquing the MD-PhDs for not doing enough research and for using the PhD-degree to climb the career ladder, while the other side emphasized the ways in which MD-PhDs increase the clinical focus on evidence-based medicine and integrate it with clinical decision making, thereby enhancing patient care. A debate is needed to establish more clearly how we wish to position MD-PhDs in the clinic, which in turn will give us a better idea of how many to educate and how to make better use of their competencies.

Inhibition of myeloid differentiation factor-2 attenuates obesity-induced cardiomyopathy and fibrosis.

PubMed

Fang, Qilu; Wang, Jingying; Zhang, Yali; Wang, Lintao; Li, Weixin; Han, Jibo; Huang, Weijian; Liang, Guang; Wang, Yi

2018-01-01

Obesity causes cardiovascular diseases, including cardiac hypertrophy and remodeling, via chronic tissue inflammation. Myeloid differentiation factor-2 (MD2), a binding protein of lipopolysaccharide, is functionally essential for the activation of proinflammatory pathways in endotoxin-induced acute inflammatory diseases. Here we tested the hypothesis that MD2 plays a central role in obesity-induced cardiomyopathy. Wildtype or MD2 knockout mice were fed with a high fat diet (HFD) or normal diet (Control) for total 16weeks, and MD2 inhibitor L6H21 (20mg/kg) or vehicle (1% CMC-Na) were administered from the beginning of the 9th week. HFD induced significant weight gain and cardiac hypertrophy, with increased cardiac fibrosis and inflammation. L6H21 administration or MD2 knockout attenuated HFD-induced obesity, inflammation and cardiac remodeling. In vitro exposure of H9C2 cells to high lipids induced cell hypertrophy with activated JNK/ERK and NF-κB pathways, which was abolished by pretreatment of MD2 inhibitor L6H21. Our results demonstrate that MD2 is essential to obesity-related cardiac hypertrophy through activating JNK/ERK and NF-κB-dependent cardiac inflammatory pathways. Targeting MD2 would be a therapeutic approach to prevent obesity-induced cardiac injury and remodeling. Copyright © 2017. Published by Elsevier B.V.

Mediodorsal nucleus of the thalamus is critical for the expression of memory of methamphetamine-produced conditioned place preference in rats.

PubMed

Kuo, C-S; Chai, S-C; Chen, H-H

2011-03-31

Methamphetamine (MA) is a powerful and highly addictive psychostimulant. However, the neural substrate mediating MA-induced conditioned effects, an essential part of addiction, remain unclear. The present study investigated the involvement of the anterior cingulate cortex (ACC), the lateral nucleus of amygdala (LNA), and the mediodorsal nucleus of the thalamus (MD) in MA-conditioned place preference (CPP). Rats underwent bilateral radio-frequency lesions of the ACC, LNA, or MD followed by MA CPP training. Lesions of the MD, but not the ACC or LNA, disrupted MA CPP learning. To clarify the role of the MD on the different stages of the MA CPP memory process, bilateral microinfusions of lidocaine into the MD were performed 5 min prior to each conditioning trial, immediately after the conditioning trial, or 5 min before the testing phase. Pretesting, but not pre- or post-conditioning, infusions of lidocaine into the MD impaired MA CPP. Furthermore, a clear preference for the previously conditioned MA paired cues was expressed when the rats were tested again 24 h after infusions of lidocaine. These results are interpreted as indicating that the MD is specifically involved in the memory retrieval process of MA associated memory which suggests the MD could have an important role in relapse in individuals suffering from MA addiction. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Enhancement of vision by monocular deprivation in adult mice.

PubMed

Prusky, Glen T; Alam, Nazia M; Douglas, Robert M

2006-11-08

Plasticity of vision mediated through binocular interactions has been reported in mammals only during a "critical" period in juvenile life, wherein monocular deprivation (MD) causes an enduring loss of visual acuity (amblyopia) selectively through the deprived eye. Here, we report a different form of interocular plasticity of vision in adult mice in which MD leads to an enhancement of the optokinetic response (OKR) selectively through the nondeprived eye. Over 5 d of MD, the spatial frequency sensitivity of the OKR increased gradually, reaching a plateau of approximately 36% above pre-deprivation baseline. Eye opening initiated a gradual decline, but sensitivity was maintained above pre-deprivation baseline for 5-6 d. Enhanced function was restricted to the monocular visual field, notwithstanding the dependence of the plasticity on binocular interactions. Activity in visual cortex ipsilateral to the deprived eye was necessary for the characteristic induction of the enhancement, and activity in visual cortex contralateral to the deprived eye was necessary for its maintenance after MD. The plasticity also displayed distinct learning-like properties: Active testing experience was required to attain maximal enhancement and for enhancement to persist after MD, and the duration of enhanced sensitivity after MD was extended by increasing the length of MD, and by repeating MD. These data show that the adult mouse visual system maintains a form of experience-dependent plasticity in which the visual cortex can modulate the normal function of subcortical visual pathways.

Which Instructional Practices Most Help First Grade Students with and without Mathematics Difficulties?

PubMed

Morgan, Paul L; Farkas, George; Maczuga, Steve

2015-06-01

We used population-based, longitudinal data to investigate the relation between mathematics instructional practices used by 1 st grade teachers in the U.S. and the mathematics achievement of their students. Factor analysis identified four types of instructional activities (i.e., teacher-directed, student-centered, manipulatives/calculators, movement/music) and eight types of specific skills taught (e.g., adding two-digit numbers). First-grade students were then classified into five groups on the basis of their fall and/or spring of kindergarten mathematics achievement-three groups with mathematics difficulties (MD) and two without MD. Regression analysis indicated that a higher percentage of MD students in 1 st grade classrooms was associated with greater use by teachers of manipulatives/calculators and movement/music to teach mathematics. Yet follow-up analysis for each of the MD and non-MD groups indicated that only teacher-directed instruction was significantly associated with the achievement of students with MD (covariate-adjusted ES s = .05-.07). The largest predicted effect for a specific instructional practice was for routine practice and drill. In contrast, for both groups of non-MD students, teacher-directed and student-centered instruction had approximately equal, statistically significant positive predicted effects (covariate-adjusted ES s = .03-.04). First-grade teachers in the U.S. may need to increase their use of teacher-directed instruction if they are to raise the mathematics achievement of students with MD.

Effect of microwave drying and oven drying on the water activity, color, phenolic compounds content and antioxidant activity of coconut husk (Cocos nucifera L.).

PubMed

Valadez-Carmona, Lourdes; Cortez-García, Rosa María; Plazola-Jacinto, Carla Patricia; Necoechea-Mondragón, Hugo; Ortiz-Moreno, Alicia

2016-09-01

The coconut ( Cocos nucifera L.) husk is basically composed by fiber and pith material and remained under-utilized. This is an important source of phenolic compounds that could be used as functional ingredients. The aim of this study was to determine the effect of: oven-drying (OD) and microwave drying (MD), on the water activity, color, phenolic compound content and antioxidant activity of coconut husk. The OD was performed at 60 °C for 12 h and MD was performed at 900 W for 10 min. The total phenolic content (TPC) in fresh coconut husk was 64.2 mg GAE/g dry wt and significant higher than observed after OD and MD of 35.8 and 45.5 mg GAE/g dry wt, respectively. Ten phenols were identified in fresh and dehydrated coconut husks. The husk MD showed an increase in the content of gallic, 4-hydroxybenzoic, ferulic and syringic acids and epicatechin compared with the fresh; while coconut husk OD and MD, showed a decrease in the content of vanillic acid, vanillin, catequin and kaempferol. The antioxidant activity decreased after both OD and MD. However, MD resulted in a better antioxidant activity in husk than OD. MD of husk resulted into better retention of preserved color, TPC and TFC than OD.

[Axial torsion and gangrene of Meckel's diverticulum: case report].

PubMed

2015-01-01

Meckel's diverticulum (MD) is the most prevalent congenital anomaly of small intestine. It develops due to the incomplete obliteration of omphalomesenterict duct which normally undergoes obliteration during the seventh week of gestation. In the majority of cases MD is asymptomatic but it may cause various complications, such as bleeding, intestinal obstruction and inflammation. Cases of umbilical sinuses, fistulas and neoplasms related with MD have been reported, but extremely rare gangrene due to its axial torsion, especially in children, as is the case of our patients. An 11-year-old boy admitted to hospital due to 24 hours epigastric pain, vomiting and malaise. After a complete physical examination, and appropriate pre-surgical laboratory and radiographic tests, surgical exploration was performed with a midline abdominal incision. On 60th cm proximal to the ileocecal valve we found a long and in a narrow based ganrenous MD with axial torsion and fibrotic cord extending from the tip of MD to the ileal mesentery. Surrounding ileum had normal appearance. A demarcation and subsequent resection of MD and the surrounding ileum was performed with end-to-end ileal anastomosis. Postoperative recovery was successful and the patient was discharged after six days. Axial torsion of MD is presented with non-specific abdominal symptoms and difficult preoperative diagnosis. The choice of diagnosis and therapy is surgical exploration and resection of MD.

Screening probiotic candidates for a mixture of probiotics to enhance the growth performance, immunity, and disease resistance of Asian seabass, Lates calcarifer (Bloch), against Aeromonas hydrophila.

PubMed

Lin, Hsueh-Li; Shiu, Ya-Li; Chiu, Chiu-Shia; Huang, Shih-Ling; Liu, Chun-Hung

2017-01-01

Six bacteria, including, Lactobacillus casei M15, Lac. plantarum D8, Lac. pentosus BD6, Lac. fermentum LW2, Enterococcus faecium 10-10, and Bacillus subtilis E20, and one yeast, Saccharomyces cerevisiae P13 were selected as probiotics for Asian seabass, Lates calcarifer, by tracking the growth performance and disease resistance of fish against Aeromonas hydrophila in the first trial. The probiotic efficiency screening results showed that B. subtilis E20 and Lac. pentosus BD6, and S. cerevisiae P13 and Lac. fermentum LW2 respectively improved either the growth performance or disease resistance. Therefore, these four probiotics were then selected to prepare a probiotics mixture, and this was incorporated in equal proportions into diets for Asian seabass at levels of 0 (control), and 10 6 (MD6), 10 7 (MD7), 10 8 (MD8), and 10 9 (MD9) colony-forming units (cfu) (kg diet) -1 . A synergistic effect of the combined probiotics was investigated in this study, and the probiotics mixture was able to improve both the growth performance and health status of fish. After 56 days of feeding, fish fed the MD9 diet had a higher final weight and percentage of weight gain. In addition, protein contents in the dorsal muscle of fish fed the MD8 and MD9 diets were significantly higher compared to the control. For the pathogen challenge test, fish fed the MD7, MD8, and MD9 diets had significantly lower cumulative mortalities after A. hydrophila infection compared to those of fish fed the control and MD6 diets, which might have been due to increased respiratory bursts, decreased superoxide dismutase activity in leucocytes, and increased phagocytic activity. Therefore, we considered that the probiotics mixture could adequately provide probiotic efficiency for Asian seabass, and the diet containing 10 9  cfu (kg diet) -1 probiotic mixture is recommended to improve the growth and health status of Asian seabass. Copyright © 2016. Published by Elsevier Ltd.

Quality of life in age-related macular degeneration: a review of the literature

PubMed Central

Mitchell, Jan; Bradley, Clare

2006-01-01

Background The Age-related Macular Degeneration Alliance International commissioned a review of the literature on quality of life (QoL) in macular degeneration (MD) with a view to increasing awareness of MD, reducing its impact and improving services for people with MD worldwide. Method A systematic review was conducted using electronic databases, conference proceedings and key journal hand search checks. The resulting 'White Paper' was posted on the AMD Alliance website and is reproduced here. Review MD is a chronic, largely untreatable eye condition which leads to loss of central vision needed for tasks such as reading, watching TV, driving, recognising faces. It is the most common cause of blindness in the Western world. Shock of diagnosis, coupled with lack of information and support are a common experience. Incidence of depression is twice that found in the community-dwelling elderly, fuelled by functional decline and loss of leisure activities. Some people feel suicidal. MD threatens independence, especially when comorbidity exacerbates functional limitations. Rehabilitation, including low vision aid (LVA) provision and training, peer support and education, can improve functional and psychological outcomes but many people do not receive services likely to benefit them. Medical treatments, suitable for only a small minority of people with MD, can improve vision but most limit progress of MD, at least for a time, rather than cure. The White Paper considers difficulties associated with inappropriate use of health status measures and misinterpretation of utility values as QoL measures: evidence suggests they have poor validity in MD. Conclusion There is considerable evidence for the major damage done to QoL by MD which is underestimated by health status and utility measures. Medical treatments are limited to a small proportion of people. However, much can be done to improve QoL by early diagnosis of MD with good communication of prognosis and continuing support. Support could include provision of LVAs, peer support, education and effective help in adjusting to MD. It is vital that appropriate measures of visual function and QoL be used in building a sound evidence base for the effectiveness of rehabilitation and treatment. PMID:17184527

High Mammographic Density in Long-Term Night-Shift Workers: DDM-Spain/Var-DDM.

PubMed

Pedraza-Flechas, Ana María; Lope, Virginia; Sánchez-Contador, Carmen; Santamariña, Carmen; Pedraz-Pingarrón, Carmen; Moreo, Pilar; Ederra, María; Miranda-García, Josefa; Vidal, Carmen; Llobet, Rafael; Aragonés, Nuria; Salas-Trejo, Dolores; Pollán, Marina; Pérez-Gómez, Beatriz

2017-06-01

Background: Night-shift work (NSW) has been suggested as a possible cause of breast cancer, and its association with mammographic density (MD), one of the strongest risk factors for breast cancer, has been scarcely addressed. This study examined NSW and MD in Spanish women. Methods: The study covered 2,752 women aged 45-68 years recruited in 2007-2008 in 7 population-based public breast cancer screening centers, which included 243 women who had performed NSW for at least one year. Occupational data and information on potential confounders were collected by personal interview. Two trained radiologist estimated the percentage of MD assisted by a validated semiautomatic computer tool (DM-scan). Multivariable mixed linear regression models with random screening center-specific intercepts were fitted using log-transformed percentage of MD as the dependent variable and adjusting by known confounding variables. Results: Having ever worked in NSW was not associated with MD [Formula: see text]:0.96; 95% confidence interval (CI), 0.86-1.06]. However, the adjusted geometric mean of the percentage of MD in women with NSW for more than 15 years was 25% higher than that of those without NSW history (MD >15 years :20.7% vs. MD never :16.5%;[Formula: see text]:1.25; 95% CI,1.01-1.54). This association was mainly observed in postmenopausal participants ([Formula: see text]:1.28; 95% CI, 1.00-1.64). Among NSW-exposed women, those with ≤2 night-shifts per week had higher MD than those with 5 to 7 nightshifts per week ([Formula: see text]:1.42; 95% CI, 1.10-1.84). Conclusions: Performing NSW was associated with higher MD only in women with more than 15 years of cumulated exposure. These findings warrant replication in futures studies. Impact: Our findings suggest that MD could play a role in the pathway between long-term NSW and breast cancer. Cancer Epidemiol Biomarkers Prev; 26(6); 905-13. ©2017 AACR . ©2017 American Association for Cancer Research.

Cognitive Functions and Neurodevelopmental Disorders Involving the Prefrontal Cortex and Mediodorsal Thalamus

PubMed Central

Ouhaz, Zakaria; Fleming, Hugo; Mitchell, Anna S.

2018-01-01

The mediodorsal nucleus of the thalamus (MD) has been implicated in executive functions (such as planning, cognitive control, working memory, and decision-making) because of its significant interconnectivity with the prefrontal cortex (PFC). Yet, whilst the roles of the PFC have been extensively studied, how the MD contributes to these cognitive functions remains relatively unclear. Recently, causal evidence in monkeys has demonstrated that in everyday tasks involving rapid updating (e.g., while learning something new, making decisions, or planning the next move), the MD and frontal cortex are working in close partnership. Furthermore, researchers studying the MD in rodents have been able to probe the underlying mechanisms of this relationship to give greater insights into how the frontal cortex and MD might interact during the performance of these essential tasks. This review summarizes the circuitry and known neuromodulators of the MD, and considers the most recent behavioral, cognitive, and neurophysiological studies conducted in monkeys and rodents; in total, this evidence demonstrates that MD makes a critical contribution to cognitive functions. We propose that communication occurs between the MD and the frontal cortex in an ongoing, fluid manner during rapid cognitive operations, via the means of efference copies of messages passed through transthalamic routes; the conductance of these messages may be modulated by other brain structures interconnected to the MD. This is similar to the way in which other thalamic structures have been suggested to carry out forward modeling associated with rapid motor responding and visual processing. Given this, and the marked thalamic pathophysiology now identified in many neuropsychiatric disorders, we suggest that changes in the different subdivisions of the MD and their interconnections with the cortex could plausibly give rise to a number of the otherwise disparate symptoms (including changes to olfaction and cognitive functioning) that are associated with many different neuropsychiatric disorders. In particular, we will focus here on the cognitive symptoms of schizophrenia and suggest testable hypotheses about how changes to MD-frontal cortex interactions may affect cognitive processes in this disorder. PMID:29467603

Distinct Facial Processing Related Negative Cognitive Bias in First-Episode and Recurrent Major Depression: Evidence from the N170 ERP Component

PubMed Central

Chen, Jiu; Ma, Wentao; Zhang, Yan; Wu, Xingqu; Wei, Dunhong; Liu, Guangxiong; Deng, Zihe; Yang, Laiqi; Zhang, Zhijun

2014-01-01

Background States of depression are associated with increased sensitivity to negative events. For this novel study, we have assessed the relationship between the number of depressive episodes and the dysfunctional processing of emotional facial expressions. Methodology/Principal Findings We used a visual emotional oddball paradigm to manipulate the processing of emotional information while event-related brain potentials were recorded in 45 patients with first episode major depression (F-MD), 40 patients with recurrent major depression (R-MD), and 46 healthy controls (HC). Compared with the HC group, F-MD patients had lower N170 amplitudes when identifying happy, neutral, and sad faces; R-MD patients had lower N170 amplitudes when identifying happy and neutral faces, but higher N170 amplitudes when identifying sad faces. F-MD patients had longer N170 latencies when identifying happy, neutral, and sad faces relative to the HC group, and R-MD patients had longer N170 latencies when identifying happy and neutral faces, but shorter N170 latencies when identifying sad faces compared with F-MD patients. Interestingly, a negative relationship was observed between N170 amplitude and the depressive severity score for identification of happy faces in R-MD patients while N170 amplitude was positively correlated with the depressive severity score for identification of sad faces in F-MD and R-MD patients. Additionally, the deficits of N170 amplitude for sad faces positively correlated with the number of depressive episodes in R-MD patients. Conclusion/Significance These results provide new evidence that having more recurrent depressive episodes and serious depressive states are likely to aggravate the already abnormal processing of emotional facial expressions in patients with depression. Moreover, it further suggests that the impaired processing as indexed by N170 amplitude for positive face identification may be a potentially useful biomarker for predicting propagation of depression while N170 amplitude for negative face identification could be a potential biomarker for depression recurrence. PMID:25314024

Comparison of sediment and nutrient export and runoff characteristics from watersheds with centralized versus distributed stormwater management.

PubMed

Hopkins, Kristina G; Loperfido, J V; Craig, Laura S; Noe, Gregory B; Hogan, Dianna M

2017-12-01

Stormwater control measures (SCMs) are used to retain stormwater and pollutants. SCMs have traditionally been installed in a centralized manner using detention to mitigate peak flows. Recently, distributed SCM networks that treat runoff near the source have been increasingly utilized. The aim of this study was to evaluate differences among watersheds that vary in SCM arrangement by assessing differences in baseflow nutrient (NO x -N and PO 4 - ) concentrations and fluxes, stormflow export of suspended sediments and particulate phosphorus (PP), and runoff characteristics. A paired watershed approach was used to compare export between 2004 and 2016 from one forested watershed (For-MD), one suburban watershed with centralized SCMs (Cent-MD), and one suburban watershed with distributed SCMs (Dist-MD). Results indicated baseflow nitrate (NO x -N) concentrations typically exceeded 1 mg-N/L in all watersheds and were highest in Dist-MD. Over the last 10 years in Dist-MD, nitrate concentrations in both stream baseflow and in a groundwater well declined as land use shifted from agriculture to suburban. Baseflow nitrate export temporarily increased during the construction phase of SCM development in Dist-MD. This temporary pulse of nitrate may be attributed to the conversion of sediment control facilities to SCMs and increased subsurface flushing as infiltration SCMs came on line. During storm flow, Dist-MD tended to have less runoff and lower maximum specific discharge than Cent-MD for small events (<1.3 cm), but runoff responses became increasingly similar to Cent-MD with increasing precipitation (>1.3 cm). Mass export estimated during paired storm events indicated Dist-MD exported 30% less sediment and 31% more PP than Cent-MD. For large precipitation events, export of sediment and PP was similar among all three watersheds. Results suggest that distributed SCMs can reduce runoff and sediment loads during small rain events compared to centralized SCMs, but these differences become less evident for large events when peak discharge likely leads to substantial bank erosion. Published by Elsevier Ltd.

Cognitive control dysfunction in emotion dysregulation and psychopathology of major depression (MD): Evidence from transcranial brain stimulation of the dorsolateral prefrontal cortex (DLPFC).

PubMed

Salehinejad, Mohammad Ali; Ghanavai, Elham; Rostami, Reza; Nejati, Vahid

2017-03-01

Previous studies showed that MD is associated with a variety of cognitive deficits and executive dysfunctions which can persist even in remitted states. However, the role of cognitive impairments in MD psychopathology and treatment is not fully understood. This article aims to discuss how executive functions central components (e.g., Working memory and attention) mediate MD psychopathology considering the role of dorsolateral prefrontal cortex (dLPFC) and present findings of a brain stimulation experiment to support this notion. The effect of transcranial direct current stimulation (tDCS) of the dLPFC on enhancing cognitive control functions was investigated. Twenty-four patients with MD (Experimental group=12, Control group=12) received 10 sessions of tDCS (2mA for 30min) over 10 consecutive days. The experimental group received active stimulation and the control group received sham stimulation. Participant's performance on cognitive functions (PAL, SRM, RVP and CRT from CANTAB) and their depression scores were assessed before and after tDCS. Results showed that brain stimulation of the dLPFC improved executive dysfunction in patients and a significant improvement on depression scores was also observed suggesting that cognitive control dysfunction may be a mediator in emotional dysregulation and psychopathology of MD. No follow-up investigation was done in this study which does not allow to infer long-term effect of tDCS. Low-focality of tDCS might have stimulated adjacent areas too. Cognitive components, namely cognitive control dysfunction, play role in MD psychopathology as they are involved in emotion dysregulation in MD. The amount of contribution of cognitive components in MD psychopathology is however, an open question. tDCS can be used as an intervention to improve cognitive dysfunction in MD. Copyright © 2017 Elsevier B.V. All rights reserved.

Common genetic variation and novel loci associated with volumetric mammographic density.

PubMed

Brand, Judith S; Humphreys, Keith; Li, Jingmei; Karlsson, Robert; Hall, Per; Czene, Kamila

2018-04-17

Mammographic density (MD) is a strong and heritable intermediate phenotype of breast cancer, but much of its genetic variation remains unexplained. We conducted a genetic association study of volumetric MD in a Swedish mammography screening cohort (n = 9498) to identify novel MD loci. Associations with volumetric MD phenotypes (percent dense volume, absolute dense volume, and absolute nondense volume) were estimated using linear regression adjusting for age, body mass index, menopausal status, and six principal components. We also estimated the proportion of MD variance explained by additive contributions from single-nucleotide polymorphisms (SNP-based heritability [h 2 SNP ]) in 4948 participants of the cohort. In total, three novel MD loci were identified (at P < 5 × 10 - 8 ): one for percent dense volume (HABP2) and two for the absolute dense volume (INHBB, LINC01483). INHBB is an established locus for ER-negative breast cancer, and HABP2 and LINC01483 represent putative new breast cancer susceptibility loci, because both loci were associated with breast cancer in available meta-analysis data including 122,977 breast cancer cases and 105,974 control subjects (P < 0.05). h 2 SNP (SE) estimates for percent dense, absolute dense, and nondense volume were 0.29 (0.07), 0.31 (0.07), and 0.25 (0.07), respectively. Corresponding ratios of h 2 SNP to previously observed narrow-sense h 2 estimates in the same cohort were 0.46, 0.72, and 0.41, respectively. These findings provide new insights into the genetic basis of MD and biological mechanisms linking MD to breast cancer risk. Apart from identifying three novel loci, we demonstrate that at least 25% of the MD variance is explained by common genetic variation with h 2 SNP /h 2 ratios varying between dense and nondense MD components.

Sulforaphane inhibits the engagement of LPS with TLR4/MD2 complex by preferential binding to Cys133 in MD2.

PubMed

Koo, Jung Eun; Park, Zee-Yong; Kim, Nam Doo; Lee, Joo Young

2013-05-10

Toll-like receptors (TLRs) are key pattern-recognition receptors that recognize invading pathogens and non-microbial endogenous molecules to induce innate and adaptive immune responses. Since activation of TLRs is deeply implicated in the pathological progress of autoimmune diseases, sepsis, metabolic diseases, and cancer, modulation of TLR activity is considered one of the most important therapeutic approaches. Lipopolysaccharide (LPS), an endotoxin of gram-negative bacteria, is a well-known agonist for TLR4 triggering inflammation and septic shock. LPS interacts with TLR4 through binding to a hydrophobic pocket in myeloid differentiation 2 (MD2), a co-receptor of TLR4. In this study, we showed that sulforaphane (SFN) interfered with the binding of LPS to MD2 as determined by in vitro binding assay and co-immunoprecipitation of MD2 and LPS in a cell system. The inhibitory effect of SFN on the interaction of LPS and MD2 was reversed by thiol supplementation with N-acetyl-L-cysteine or dithiothreitol showing that the inhibitory effect of SFN is dependent on its thiol-modifying activity. Indeed, micro LC-MS/MS analysis showed that SFN preferentially formed adducts with Cys133 in the hydrophobic pocket of MD2, but not with Cys95 and Cys105. Molecular modeling showed that SFN bound to Cys133 blocks the engagement of LPS and lipid IVa to hydrophobic pocket of MD2. Our results demonstrate that SFN interrupts LPS engagement to TLR4/MD2 complex by direct binding to Cys133 in MD2. Our data suggest a novel mechanism for the anti-inflammatory activity of SFN, and provide a novel target for the regulation of TLR4-mediated inflammatory and immune responses by phytochemicals. Copyright © 2013 Elsevier Inc. All rights reserved.

Failure to launch: the self-regulating Md-MYB10 R6 gene from apple is active in flowers but not leaves of Petunia.

PubMed

Boase, Murray R; Brendolise, Cyril; Wang, Lei; Ngo, Hahn; Espley, Richard V; Hellens, Roger P; Schwinn, Kathy E; Davies, Kevin M; Albert, Nick W

2015-10-01

The Md - MYB10 R6 gene from apple is capable of self-regulating in heterologous host species and enhancing anthocyanin pigmentation, but the activity of MYB10 is dependent on endogenous protein partners. Coloured foliage due to anthocyanin pigments (bronze/red/black) is an attractive trait that is often lacking in many bedding, ornamental and horticultural plants. Apples (Malus × domestica) containing an allelic variant of the anthocyanin regulator, Md-MYB10 R6 , are highly pigmented throughout the plant, due to autoregulation by MYB10 upon its own promoter. We investigated whether Md-MYB10 R6 from apple is capable of functioning within the heterologous host Petunia hybrida to generate plants with novel pigmentation patterns. The Md-MYB10 R6 transgene (MYB10-R6 pro :MYB10:MYB10 term ) activated anthocyanin synthesis when transiently expressed in Antirrhinum rosea (dorsea) petals and petunia leaf discs. Stable transgenic petunias containing Md-MYB10 R6 lacked foliar pigmentation but had coloured flowers, complementing the an2 phenotype of 'Mitchell' petunia. The absence of foliar pigmentation was due to the failure of the Md-MYB10 R6 gene to self-activate in vegetative tissues, suggesting that additional protein partners are required for Md-MYB10 to activate target genes in this heterologous system. In petunia flowers, where endogenous components including MYB-bHLH-WDR (MBW) proteins were present, expression of the Md-MYB10 R6 promoter was initiated, allowing auto-regulation to occur and activating anthocyanin production. Md-MYB10 is capable of operating within the petunia MBW gene regulation network that controls the expression of the anthocyanin biosynthesis genes, AN1 (bHLH) and MYBx (R3-MYB repressor) in petals.

Comparison of outpatient and home-based exercise training programmes for COPD: A systematic review and meta-analysis.

PubMed

Wuytack, Francesca; Devane, Declan; Stovold, Elizabeth; McDonnell, Melissa; Casey, Michelle; McDonnell, Timothy J; Gillespie, Paddy; Raymakers, Adam; Lacasse, Yves; McCarthy, Bernard

2018-03-01

Chronic obstructive pulmonary disease is a common, preventable and treatable disease. Exercise training programmes (ETPs) improve symptoms, health-related quality of life (HRQoL) and exercise capacity, but the optimal setting is unknown. In this review, we compared the effects of ETPs in different settings on HRQoL and exercise capacity. We searched (5 July 2016) the Cochrane Airways Group Specialised Register, ClinicalTrials.gov and World Health Organization trials portal. We selected studies, extracted data and assessed risk of bias with two independent reviewers. We calculated mean differences (MD) with 95% CI. We assessed the quality of evidence using Grades of Recommendation, Assessment, Development and Evaluation. Ten trials (934 participants) were included. Hospital (outpatient) and home-based ETPs (seven trials) were equally effective at improving HRQoL on the Chronic Respiratory Questionnaire (CRQ) (dyspnoea: MD -0.09, 95% CI: -0.28 to 0.10; fatigue: MD -0.00, 95% CI: -0.18 to 0.17; emotional: MD 0.10, 95% CI: -0.24 to 0.45; and mastery: MD -0.02, 95% CI: -0.28 to 0.25; moderate quality) and on the St George's Respiratory Questionnaire (SGRQ) (MD -0.82, 95% CI: -7.47 to 5.83, low quality). Hospital (outpatient) and community-based ETPs (three trials) were equally effective at improving HRQoL (CRQ dyspnoea: MD 0.29, 95% CI: -0.05 to 0.62, moderate quality; fatigue: MD -0.02, 95% CI: -1.09 to 1.05, low quality; emotional: MD 0.10, 95% CI: -0.40 to 0.59, moderate quality; and mastery: MD -0.08, 95% CI: -0.45 to 0.28, moderate quality). There was no difference in exercise capacity. There was low to moderate evidence that outpatient and home-based ETPs are equally effective. See related Editorial. © 2017 Asian Pacific Society of Respirology.

Identification of moisture content in tobacco plant leaves using outlier sample eliminating algorithms and hyperspectral data.

PubMed

Sun, Jun; Zhou, Xin; Wu, Xiaohong; Zhang, Xiaodong; Li, Qinglin

2016-02-26

Fast identification of moisture content in tobacco plant leaves plays a key role in the tobacco cultivation industry and benefits the management of tobacco plant in the farm. In order to identify moisture content of tobacco plant leaves in a fast and nondestructive way, a method involving Mahalanobis distance coupled with Monte Carlo cross validation(MD-MCCV) was proposed to eliminate outlier sample in this study. The hyperspectral data of 200 tobacco plant leaf samples of 20 moisture gradients were obtained using FieldSpc(®) 3 spectrometer. Savitzky-Golay smoothing(SG), roughness penalty smoothing(RPS), kernel smoothing(KS) and median smoothing(MS) were used to preprocess the raw spectra. In addition, Mahalanobis distance(MD), Monte Carlo cross validation(MCCV) and Mahalanobis distance coupled to Monte Carlo cross validation(MD-MCCV) were applied to select the outlier sample of the raw spectrum and four smoothing preprocessing spectra. Successive projections algorithm (SPA) was used to extract the most influential wavelengths. Multiple Linear Regression (MLR) was applied to build the prediction models based on preprocessed spectra feature in characteristic wavelengths. The results showed that the preferably four prediction model were MD-MCCV-SG (Rp(2) = 0.8401 and RMSEP = 0.1355), MD-MCCV-RPS (Rp(2) = 0.8030 and RMSEP = 0.1274), MD-MCCV-KS (Rp(2) = 0.8117 and RMSEP = 0.1433), MD-MCCV-MS (Rp(2) = 0.9132 and RMSEP = 0.1162). MD-MCCV algorithm performed best among MD algorithm, MCCV algorithm and the method without sample pretreatment algorithm in the eliminating outlier sample from 20 different moisture gradients of tobacco plant leaves and MD-MCCV can be used to eliminate outlier sample in the spectral preprocessing. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular cloning and functional analysis of a UV-B photoreceptor gene, MdUVR8 (UV Resistance Locus 8), from apple.

PubMed

Zhao, Cheng; Mao, Ke; You, Chun-Xiang; Zhao, Xian-Yan; Wang, Shu-Hui; Li, Yuan-Yuan; Hao, Yu-Jin

2016-06-01

UVR8 (UV Resistance Locus 8) is an ultraviolet-B (UV-B; 280-315nm) light receptor that is involved in regulating many aspects of plant growth and development. UV-B irradiation can increase the development of flower and fruit coloration in many fruit trees, such as grape, pear and apple. Previous investigations of the structure and functions of UVR8 in plants have largely focused on Arabidopsis. Here, we isolated the UVR8 gene from apple (Malus domestica) and analyzed its function in transgenic Arabidopsis. Genomic and protein sequence analysis showed that MdUVR8 shares high similarity with the AtUVR8 protein from Arabidopsis, including the conserved seven-bladed β-propeller, the C27 region, the 3 "GWRHT" motifs and crucial amino-acid residues (14 Trps, 2 Args). A point mutation prediction and three-dimensional structural analysis of MdUVR8 indicated that it has a similar structure to AtUVR8 and that the crucial residues are also important in MdUVR8. In terms of transcript levels, MdUVR8 expression was up-regulated by UV-B light, which suggests that its expression follows a 24-h circadian rhythm. Using heterologous expression of MdUVR8 in both uvr8-1 mutant and wild-type (WT) Arabidopsis, we found that MdUVR8 regulates hypocotyl elongation and gene expression under UV-B light. These data provide functional evidence for a role of MdUVR8 in controlling photomorphogenesis under UV-B light and indicate that the function of UVR8 is conserved between Arabidopsis and apple. Furthermore, we examined the interaction between MdUVR8 and MdCOP1 (constitutive photomorphogenic1) using a yeast two-hybrid assay and a co-immunoprecipitation assay. This interaction provides a direction for investigating the regulatory mechanisms of the UV-B-light pathway in apple. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Summary of the 2016 Partners Against Mortality in Epilepsy (PAME) Conference.

PubMed

2016-01-01

Authors: Kevin D Graber, MD, Jeffrey Buchhalter, MD, PhD, Elson So, MD, Rainer Surges, MD, Detlev Boison, PhD, Franck Kalume, PhD, Cyndi Wright, Brian Gehlbach, MD, Jeff Noebels, MD, PhD, Vicky Whittemore, PhD, Elizabeth J. Donner, MD, MSc, Tom Stanton, MPP, Henry Smithson, MD, Jane Hanna, Masud Seyal, MD, PhD, Philippe Ryvlin, MD, PhD The third biannual Partners Against Mortality in Epilepsy (PAME) conference was held in Alexandria, VA from June 23-26, 2016. This was an intimate meeting of clinical and basic scientists, clinicians, people affected by Sudden Unexpected Death in Epilepsy Patients (SUDEP) in a loved one, people living with epilepsy and patient advocate organizations. Plenary sessions have been summarized by moderators, including: 1) Mortality in people with epilepsy: epidemiology and surveillance. 2) Mortality in children. 3) What do we know about the factors that predispose certain people to die from a seizure? 4) What are the events that occur during and after a seizure that cause a death in SUDEP? 5) What are the options for prevention now and in the future? 6) Advocacy perspectives: how can we speed up awareness and prevention? 7) Updates and discussion on select programs in mortality research. Breakout sessions allowed for a more focused audience. Those summarized here are: Frequent non-SUDEP causes of mortality in people with epilepsy; Mechanisms of SUDEP; Lessons learned in grief and how to better support families; Future directions for research to impact prevention; and How do we improve SUDEP risk disclosure? While significant progress has been made with review of human mortality in epilepsy and study of animal models, this meeting emphasized the need for: better understandings of the epidemiology of SUDEP, advances in the understandings of mechanisms, continued search for biomarkers and preventative measures, patient education, increased awareness, continued advocacy for patient and family support and research funding.

A novel matrix dispersion based on phospholipid complex for improving oral bioavailability of baicalein: preparation, in vitro and in vivo evaluations.

PubMed

Zhou, Yang; Dong, Wujun; Ye, Jun; Hao, Huazhen; Zhou, Junzhuo; Wang, Renyun; Liu, Yuling

2017-11-01

Phospholipid complex is one of the most successful approaches for enhancing oral bioavailability of poorly absorbed plant constituents. But the sticky property of phospholipids results in an unsatisfactory dissolution of drugs. In this study, a matrix dispersion of baicalein based on phospholipid complex (BaPC-MD) was first prepared by a discontinuous solvent evaporation method, in which polyvinylpyrrolidone-K30 (PVP-K30) was employed for improving the dispersibility of baicalein phospholipid complex (BaPC) and increasing dissolution of baicalein. The combination ratio of baicalein and phospholipids in BaPC-MD was 99.39% and baicalein was still in a complete complex state with phospholipid in BaPC-MD. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier Transform Infrared (FTIR) analyzes demonstrated that baicalein was fully transformed to an amorphous state in BaPC-MD and phospholipid complex formed. The water-solubility and n-octanol solubility of baicalein in BaPC-MD significantly increased compared with those of pure baicalein. Compared with baicalein and BaPC, the cumulative dissolution of BaPC-MD at 120 min increased 2.77- and 1.23-fold, respectively. In vitro permeability study in Caco-2 cells indicated that the permeability of BaPC-MD was remarkably higher than those of baicalein and BaPC. Pharmacokinetic study showed that the average C max of BaPC-MD was significantly increased compared to baicalein and BaPC. AUC 0-14 h of BaPC-MD was 5.01- and 1.91-fold of baicalein and BaPC, respectively. The novel BaPC-MD significantly enhanced the oral bioavailability of baicalein by improving the dissolution and permeability of baicalein without destroying the complexation state of baicalein and phospholipids. The current drug delivery system provided an optimal strategy to significantly enhance oral bioavailability for poorly water-soluble drugs.

A Highly Parallelized Special-Purpose Computer for Many-Body Simulations with an Arbitrary Central Force: MD-GRAPE

NASA Astrophysics Data System (ADS)

Fukushige, Toshiyuki; Taiji, Makoto; Makino, Junichiro; Ebisuzaki, Toshikazu; Sugimoto, Daiichiro

1996-09-01

We have developed a parallel, pipelined special-purpose computer for N-body simulations, MD-GRAPE (for "GRAvity PipE"). In gravitational N- body simulations, almost all computing time is spent on the calculation of interactions between particles. GRAPE is specialized hardware to calculate these interactions. It is used with a general-purpose front-end computer that performs all calculations other than the force calculation. MD-GRAPE is the first parallel GRAPE that can calculate an arbitrary central force. A force different from a pure 1/r potential is necessary for N-body simulations with periodic boundary conditions using the Ewald or particle-particle/particle-mesh (P^3^M) method. MD-GRAPE accelerates the calculation of particle-particle force for these algorithms. An MD- GRAPE board has four MD chips and its peak performance is 4.2 GFLOPS. On an MD-GRAPE board, a cosmological N-body simulation takes 6O0(N/10^6^)^3/2^ s per step for the Ewald method, where N is the number of particles, and would take 24O(N/10^6^) s per step for the P^3^M method, in a uniform distribution of particles.

Constant-pH molecular dynamics using stochastic titration

NASA Astrophysics Data System (ADS)

Baptista, António M.; Teixeira, Vitor H.; Soares, Cláudio M.

2002-09-01

A new method is proposed for performing constant-pH molecular dynamics (MD) simulations, that is, MD simulations where pH is one of the external thermodynamic parameters, like the temperature or the pressure. The protonation state of each titrable site in the solute is allowed to change during a molecular mechanics (MM) MD simulation, the new states being obtained from a combination of continuum electrostatics (CE) calculations and Monte Carlo (MC) simulation of protonation equilibrium. The coupling between the MM/MD and CE/MC algorithms is done in a way that ensures a proper Markov chain, sampling from the intended semigrand canonical distribution. This stochastic titration method is applied to succinic acid, aimed at illustrating the method and examining the choice of its adjustable parameters. The complete titration of succinic acid, using constant-pH MD simulations at different pH values, gives a clear picture of the coupling between the trans/gauche isomerization and the protonation process, making it possible to reconcile some apparently contradictory results of previous studies. The present constant-pH MD method is shown to require a moderate increase of computational cost when compared to the usual MD method.

Association of past and recent major depression and menstrual characteristics in midlife: Study of Women's Health Across the Nation.

PubMed

Bromberger, Joyce T; Schott, Laura L; Matthews, Karen A; Kravitz, Howard M; Randolph, John F; Harlow, Sioban; Crawford, Sybil; Green, Robin; Joffe, Hadine

2012-09-01

The aim of this study was to examine the association of a history of major depression (MD) with menstrual problems in a multiethnic sample of midlife women. Participants were 934 women enrolled in the Study of Women's Health Across the Nation, a multisite study of menopause and aging. The outcomes were menstrual bleeding problems and premenstrual symptoms in the year before study entry. The Structured Clinical Interview for the Diagnosis of DSM-IV Axis I Disorders was conducted to determine recent and past psychiatric diagnoses. Covariates included sociodemographic, behavioral, and gynecologic factors. One third of the participants reported heavy bleeding, 20% reported other abnormal bleeding, and 18% reported premenstrual symptoms. One third had past and 11% had recent MD. Past MD was associated with an increased likelihood of heavy bleeding (odds ratio, 1.89; 95% CI, 1.25-2.85), adjusting for recent MD, menopause status, and other covariates. Past MD was not associated with other abnormal bleeding or premenstrual symptoms in the final analysis that adjusted for recent MD. Midlife women with a history of MD are more likely to report heavy bleeding.

The prevalence, clinical correlates and structure of phobic fears in Han Chinese women with recurrent major depression.

PubMed

Yang, Fuzhong; Qiu, Jianyin; Zhao, Hongsu; Wang, Zhoubing; Tao, Danhong; Xiao, Xue; Niu, Qihui; Wang, Qian; Li, Yajuan; Guo, Liyang; Li, Jianying; Li, Kan; Xia, Jing; Wang, Lina; Shang, Xiaofang; Sang, Wenhua; Gan, Zhaoyu; He, Kangmei; Zhao, Xiaochuan; Tian, Tian; Xu, Dan; Gu, Danhua; Weng, Xiaoqin; Li, Haimin; Tian, Jing; Yang, Lijun; Li, Qiang; Yang, Qingzhen; Wang, Hui; Dang, Yamei; Dai, Lei; Cui, Yanping; Ye, Dong; Cao, Juling; Guo, Li; Kang, Zhen; Liu, Jimeng; Chen, Bin; Liu, Jinhua; Zhang, Jinling; Yang, Donglin; Jiao, Bin; Yu, Fengyu; Geng, Feng; Li, Ling; Yang, Haiying; Dai, Hong; Wang, Hongli; Liu, Caixing; Liu, Haijun; Peng, Longyan; Wang, Xiaoping; Wei, Shaojun; Liu, Xiaojuan; Li, Chang; Liu, Zhengrong; Zhang, Qiwen; Di, Dongchuan; Shi, Shenxun; Flint, Jonathan; Kendler, Kenneth S

2014-03-01

Phobic fears are common in the general population and among individuals with major depression (MD). We know little about the prevalence, clinical correlates, and structure of phobic fears in Chinese women with MD. We assessed 22 phobic fears in 6017 Han Chinese women with MD. We used exploratory factor analysis to examine the structure of these phobic fears. We examined the relationship between individual phobic fears and the severity of MD, neuroticism, comorbid panic disorder, generalized anxiety disorder and dysthymia using logistic regression models. The frequency of phobic fears ranged from 3.0% (eating in public) to 36.0% (snakes). Phobic fears were significantly associated with more severe MD, high neuroticism, and co-morbid panic disorder, generalized anxiety disorder and dysthymia. Our factor analysis suggested four underlying subgroups of phobic fears which differed in their clinical correlates, severity and patterns of comorbidity. Data were collected retrospectively through interview and recall bias may have affected the results. Phobic fears are correlated with comorbid MD and more severe MD. These phobic fears clearly subdivide into four subgroups that differ meaningfully from each other. Copyright © 2014 Elsevier B.V. All rights reserved.

Summary of breakout session f: facility and equipment decontamination strategies.

PubMed

Norwood, Laurie P; Suvarna, Kalavati

2011-01-01

CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA).

76 FR 53021 - Public Hearing and Commission Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-24

... Water Supply System, Halls Cross Roads District, Harford County, Md. Modification to conditions of the... Baltimore. Project Facility: Maryland Water Supply System, Halls Cross Roads District, Harford County, Md... Facility: Maryland Water Supply System, Halls Cross Roads District, Harford County, Md. Modification to...

77 FR 54919 - National Institute on Drug Abuse; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-06

... Institutes of Health; Neuroscience Center, 6001 Executive Boulevard, Rockville, MD 20852. Contact Person... Institutes of Health, Neuroscience Center, 6001 Executive Boulevard, Rockville, MD 20852. Contact Person...: National Institutes of Health, Neuroscience Center, 6001 Executive Boulevard, Rockville, MD 20852, (Virtual...

A System Approach to Navy Medical Education and Training. Volume 1

DTIC Science & Technology

1974-08-31

each of the four major pro - ducts complement one another, they form, in fact, a single major product, that of the technology for improved training...the course of determining the functional limits and con - tent areas peculiar to potentially delegable tasks, it is highly desirable to be able to...NISTOS CYTO CLINICAL X-RAY LAS AST LAB ASST LAB AS SI AS SL ABI ASITO LA LAB STMIL OPERATIONS PATIENT CARE OP -- PC -- GMo GMO M.D. M.D. M.D MD M

Prospective Study of Respiratory Infections at the U.S. Naval Academy

DTIC Science & Technology

2001-09-01

conducting the .findings were significant in demonstrating infection cause and study at the U.S. Naval Academy: Tomoko Hooper, MD MPH; Richard Jhe large...leven M, Ursi D, Van Bever H, Quint W, Niesters HG, Goossens H: Detection of disease. J Infect Dis 1992; 166: 365-73. Mycoplasmapneumoniaeby two...6. AUTHORS 5d. Project Number: Gregory C. Gray, MD, MPH; Robert G. Schultz, MD; Gary D. Gackstetter, DVM, 5e. Task Number: PhD; Richard Thomas, MD

Center for the Study of Traumatic Stress 2010 Annual Report: Improving Psychological Health and Resilience Through Trauma Research, Education and Consultation

DTIC Science & Technology

2011-01-01

Health Sciences 4301 Jones Bridge Road Bethesda, MD 20814-4799 Craig H. Llewellyn , M.D. professor Department of Military and emergency Medicine F...Health Sciences,4301 Jones Bridge Road,Bethesda,MD,20814-4799 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND...F. edward Hebert School of Medicine uniformed Services university 4301 Jones Bridge Road Bethesda, MD20814-4799 BG (ret) William T. Bester, RN, MSN

Outcomes of Bacteremia in Burn Patients Involved in Combat Operations Overseas

DTIC Science & Technology

2008-03-01

MD, Mark S Rasnake, MD, Duane R Hospenthal, MD, PhD, FACP, Steven E Wolf, MD, FACS BACKGROUND: Burn patients constitute approximately 5% of...GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) Ressner R. A., Murray C. K., Griffith M. E., Rasnake M. S ., Hospenthal D. R., Wolf S . E...5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) United States Army Institute of Surgical

Accuracy of three-dimensional dental resin models created by fused deposition modeling, stereolithography, and Polyjet prototype technologies: A comparative study.

PubMed

Rebong, Raymund E; Stewart, Kelton T; Utreja, Achint; Ghoneima, Ahmed A

2018-05-01

The aim of this study was to assess the dimensional accuracy of fused deposition modeling (FDM)-, Polyjet-, and stereolithography (SLA)-produced models by comparing them to traditional plaster casts. A total of 12 maxillary and mandibular posttreatment orthodontic plaster casts were selected from the archives of the Orthodontic Department at the Indiana University School of Dentistry. Plaster models were scanned, saved as stereolithography files, and printed as physical models using three different three-dimensional (3D) printers: Makerbot Replicator (FDM), 3D Systems SLA 6000 (SLA), and Objet Eden500V (Polyjet). A digital caliper was used to obtain measurements on the original plaster models as well as on the printed resin models. Comparison between the 3D printed models and the plaster casts showed no statistically significant differences in most of the parameters. However, FDM was significantly higher on average than were plaster casts in maxillary left mixed plane (MxL-MP) and mandibular intermolar width (Md-IMW). Polyjet was significantly higher on average than were plaster casts in maxillary intercanine width (Mx-ICW), mandibular intercanine width (Md-ICW), and mandibular left mixed plane (MdL-MP). Polyjet was significantly lower on average than were plaster casts in maxillary right vertical plane (MxR-vertical), maxillary left vertical plane (MxL-vertical), mandibular right anteroposterior plane (MdR-AP), mandibular right vertical plane (MdR-vertical), and mandibular left vertical plane (MdL-vertical). SLA was significantly higher on average than were plaster casts in MxL-MP, Md-ICW, and overbite. SLA was significantly lower on average than were plaster casts in MdR-vertical and MdL-vertical. Dental models reconstructed by FDM technology had the fewest dimensional measurement differences compared to plaster models.

Variations in Patterns of Utilization and Charges for the Care of Low Back Pain in North Carolina, 2000 to 2009: A Statewide Claims' Data Analysis.

PubMed

Hurwitz, Eric L; Li, Dongmei; Guillen, Jenni; Schneider, Michael J; Stevans, Joel M; Phillips, Reed B; Phelan, Shawn P; Lewis, Eugene A; Armstrong, Richard C; Vassilaki, Maria

2016-05-01

The purpose of the study was to compare utilization and charges generated by medical doctors (MD), doctors of chiropractic (DC) and physical therapists (PT) by patterns of care for the treatment of low back pain in North Carolina. This was an analysis of low-back-pain-related closed claim data from the North Carolina State Health Plan for Teachers and State Employees from 2000 to 2009. Data were extracted from Blue Cross Blue Shield of North Carolina for the North Carolina State Health Plan using International Classification of Diseases, 9th Revision diagnostic codes for uncomplicated low back pain (ULBP) and complicated low back pain (CLBP). Care patterns with single-provider types and no referrals incurred the least charges on average for both ULBP and CLBP. When care did not include referral providers or services, for ULBP, MD and DC care was on average $465 less than MD and PT care. For CLBP, MD and DC care averaged $965 more than MD and PT care. However, when care involved referral providers or services, MD and DC care was on average $1600 less when compared to MD and PT care for ULBP and $1885 less for CLBP. Risk-adjusted charges (available 2006-2009) for patients in the middle quintile of risk were significantly less for DC care patterns. Chiropractic care alone or DC with MD care incurred appreciably fewer charges for ULBP than MD care with or without PT care. This finding was reversed for CLBP. Adjusted charges for both ULBP and CLBP patients were significantly lower for DC patients. Copyright © 2016 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

Perimetric measurements with flicker-defined form stimulation in comparison with conventional perimetry and retinal nerve fiber measurements.

PubMed

Horn, Folkert K; Tornow, Ralf P; Jünemann, Anselm G; Laemmer, Robert; Kremers, Jan

2014-04-11

We compared the results of flicker-defined form (FDF) perimetry with standard automated perimetry (SAP) and retinal nerve fiber layer (RNFL) thickness measurements using spectral domain optical coherence tomography (OCT). A total of 64 healthy subjects, 45 ocular hypertensive patients, and 97 "early" open-angle glaucoma (OAG) patients participated in this study. Definition of glaucoma was based exclusively on glaucomatous optic disc appearance. All subjects underwent FDF perimetry, SAP, and peripapillary measurements of the RNFL thickness. The FDF perimetry and SAP were performed at identical test locations (G1 protocol). Exclusion criteria were subjects younger than 34 years, SAP mean defect (SAP MD) > 5 dB, eye diseases other than glaucoma, or nonreliable FDF measurements. The correlations between the perimetric data on one hand and RNFL thicknesses on the other hand were analyzed statistically. The age-corrected sensitivity values and the local results from the controls were used to determine FDF mean defect (FDF MD). The FDF perimetry and SAP showed high concordance in this cohort of experienced patients (MD values, R = -0.69, P < 0.001). Of a total of 42 OAG patients with abnormal SAP MD, 38 also displayed abnormal FDF MD. However, FDF MD was abnormal in 28 of 55 OAG patients with normal SAP MD. The FDF MD was significantly (R = -0.61, P < 0.001) correlated with RNFL thickness with a (nonsignificantly) larger correlation coefficient than conventional SAP MD (R = -0.48, P < 0.001). The FDF perimetry is able to uncover functional changes concurrent with the changes in RNFL thickness. The FDF perimetry may be an efficient functional test to detect early glaucomatous nerve atrophy. (ClinicalTrials.gov number, NCT00494923.).

Bone mineral density and mammographic density in Mexican women.

PubMed

Moseson, Heidi; Rice, Megan S; López-Ridaura, Ruy; Bertrand, Kimberly A; Torres, Gabriela; Blanco, Margarita; Tamayo-Orozco, Juan Alfredo; Lajous, Martin; Romieu, Isabelle

2016-01-01

Bone mineral density (BMD) is a putative marker for lifetime exposure to estrogen. Studies that have explored whether BMD is a determinant of mammographic density (MD) have observed inconsistent results. Therefore,we examined this potential association in a sample of women (n = 1,516) from the clinical sub-cohort in the Mexican teachers’ cohort (n = 115,315). We used multivariable linear regression to assess the association between quartiles of BMD and percent MD, as well as total dense and non-dense area of the breast, stratified by menopausal status. We also examined the associations by body mass index (BMI) (< 30 kg/m(2), ≥ 30 kg/m(2)). Overall, there was no association between BMD and MD among premenopausal women. However, when we stratified by BMI, there was a modest inverse association between BMD and percent MD (difference between extreme quartiles = -2.8, 95 % CI -5.9, 0.27, p trend = 0.04) among women with BMI < 30 kg/m(2), but a positive association among obese women (comparable difference = 5.1, 95 % CI 0.02, 10.1, p trend = 0.03;p interaction < 0.01). Among postmenopausal women, BMD and percent MD were positively associated after adjustment for BMI (p trend < 0.01). Postmenopausal women in the highest two quartiles of BMD had 4–5 % point higher percent MD compared to women in the lowest quartile. The association did not differ by BMI in postmenopausal women (p interaction = 0.76). Among obese premenopausal women as well as postmenopausal women, BMD was positively associated with percent MD. Among leaner premenopausal women, BMD and percent MD were modestly inversely associated. These findings support the hypothesis that cumulative exposure to estrogen (as measured by BMD) may influence MD.

Individual mediodorsal thalamic neurons project to multiple areas of the rat prefrontal cortex: A single neuron-tracing study using virus vectors.

PubMed

Kuramoto, Eriko; Pan, Shixiu; Furuta, Takahiro; Tanaka, Yasuhiro R; Iwai, Haruki; Yamanaka, Atsushi; Ohno, Sachi; Kaneko, Takeshi; Goto, Tetsuya; Hioki, Hiroyuki

2017-01-01

The prefrontal cortex has an important role in a variety of cognitive and executive processes, and is generally defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD). The rat MD is mainly subdivided into three segments, the medial (MDm), central (MDc), and lateral (MDl) divisions, on the basis of the cytoarchitecture and chemoarchitecture. The MD segments are known to topographically project to multiple prefrontal areas at the population level: the MDm mainly to the prelimbic, infralimbic, and agranular insular areas; the MDc to the orbital and agranular insular areas; and the MDl to the prelimbic and anterior cingulate areas. However, it is unknown whether individual MD neurons project to single or multiple prefrontal cortical areas. In the present study, we visualized individual MD neurons with Sindbis virus vectors, and reconstructed whole structures of MD neurons. While the main cortical projection targets of MDm, MDc, and MDl neurons were generally consistent with those of previous results, it was found that individual MD neurons sent their axon fibers to multiple prefrontal areas, and displayed various projection patterns in the target areas. Furthermore, the axons of single MD neurons were not homogeneously spread, but were rather distributed to form patchy axon arbors approximately 1 mm in diameter. The multiple-area projections and patchy axon arbors of single MD neurons might be able to coactivate cortical neuron groups in distant prefrontal areas simultaneously. Furthermore, considerable heterogeneity of the projection patterns is likely, to recruit the different sets of cortical neurons, and thus contributes to a variety of prefrontal functions. J. Comp. Neurol. 525:166-185, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Wnt4 coordinates directional cell migration and extension of the Müllerian duct essential for ontogenesis of the female reproductive tract

PubMed Central

Prunskaite-Hyyryläinen, Renata; Skovorodkin, Ilya; Xu, Qi; Miinalainen, Ilkka; Shan, Jingdong; Vainio, Seppo J.

2016-01-01

The Müllerian duct (MD) is the anlage of the oviduct, uterus and upper part of the vagina, the main parts of the female reproductive tract. Several wingless-type mouse mammary tumor virus (MMTV) integration site family member (Wnt) genes, including Wnt4, Wnt5a and Wnt7a, are involved in the development of MD and its derivatives, with Wnt4 particularly critical, since the MD fails to develop in its absence. We use, here, Wnt4EGFPCre-based fate mapping to demonstrate that the MD tip cells and the subsequent MD cells are derived from Wnt4+ lineage cells. Moreover, Wnt4 is required for the initiation of MD-forming cell migration. Application of anti-Wnt4 function-blocking antibodies after the initiation of MD elongation indicated that Wnt4 is necessary for the elongation as well, and consistent with this, cell culture wound-healing assays with NIH3T3 cells overexpressing Wnt4 promoted cell migration by comparison with controls. In contrast to the Wnt4 null embryos, some Wnt4monomeric cherry/monomeric cherry (Wnt4mCh/mCh) hypomorphic mice survived to adulthood and formed MD in ∼45% of cases. Nevertheless, the MD of the Wnt4mCh/mCh females had altered cell polarization and basement membrane deposition relative to the controls. Examination of the reproductive tract of the Wnt4mCh/mCh females indicated a poorly coiled oviduct, absence of the endometrial glands and an undifferentiated myometrium, and these mice were prone to develop a hydro-uterus. In conclusion, the results suggest that the Wnt4 gene encodes signals that are important for various aspects of female reproductive tract development. PMID:26721931

Herpes virus and Ménière's disease.

PubMed

Gartner, M; Bossart, W; Linder, T

2008-01-01

The main goal of this study was to examine the vestibular ganglia from patients with intractable classic Ménière's disease (MD) for the presence or absence of DNA from three neurotropic viruses herpes simplex virus 1 and 2 (HSV1, HSV2) and varicella zoster virus (VZV) and to investigate the hypothesis that MD is associated with virus reactivation within Scarpa's ganglion. Polymerase chain reaction (PCR) was performed with nested primer sets specific for viral genomic DNA of HSV1, HSV2 and VZV in biopsies of the ganglion scarpae of patients with MD who underwent vestibular neurectomy. Included were patients with MD classified as definite MD according to American Academy of Otolaryngology/Head and Neck Surgery criteria. The ganglion scarpae and ganglion geniculi harvested at autopsy from patients without history of MD or facial palsy served as control specimens. No viral DNA was detected in the vestibular ganglion of 7 patients with definite MD. In 34% of the vestibular ganglia of the control group we detected either HSV1 or VZV. Only one Scarpa's ganglion had both viruses present at the same time. Thirty-two out of 34 ganglia from the geniculate segment of the facial nerve contained either HSV1 and/or VZV genomic DNA. Eight specimens contained both viruses simultaneously. Altogether viral DNA was found in 94% of ganglia. Viral genomic DNA of HSV2 was not detected. Although HSV and VZV appear to be present in many ganglion cells throughout the human body, we were unable to find genomic DNA of these viruses in patients with definite MD and disabling vertigo, who underwent vestibular neurectomy. Based on these results, reactivation of HSV1 and VZV in the vestibular ganglion does not seem to play a role in the pathogenesis of MD. (c) 2008 S. Karger AG, Basel

Toward ab initio molecular dynamics modeling for sum-frequency generation spectra; an efficient algorithm based on surface-specific velocity-velocity correlation function.

PubMed

Ohto, Tatsuhiko; Usui, Kota; Hasegawa, Taisuke; Bonn, Mischa; Nagata, Yuki

2015-09-28

Interfacial water structures have been studied intensively by probing the O-H stretch mode of water molecules using sum-frequency generation (SFG) spectroscopy. This surface-specific technique is finding increasingly widespread use, and accordingly, computational approaches to calculate SFG spectra using molecular dynamics (MD) trajectories of interfacial water molecules have been developed and employed to correlate specific spectral signatures with distinct interfacial water structures. Such simulations typically require relatively long (several nanoseconds) MD trajectories to allow reliable calculation of the SFG response functions through the dipole moment-polarizability time correlation function. These long trajectories limit the use of computationally expensive MD techniques such as ab initio MD and centroid MD simulations. Here, we present an efficient algorithm determining the SFG response from the surface-specific velocity-velocity correlation function (ssVVCF). This ssVVCF formalism allows us to calculate SFG spectra using a MD trajectory of only ∼100 ps, resulting in the substantial reduction of the computational costs, by almost an order of magnitude. We demonstrate that the O-H stretch SFG spectra at the water-air interface calculated by using the ssVVCF formalism well reproduce those calculated by using the dipole moment-polarizability time correlation function. Furthermore, we applied this ssVVCF technique for computing the SFG spectra from the ab initio MD trajectories with various density functionals. We report that the SFG responses computed from both ab initio MD simulations and MD simulations with an ab initio based force field model do not show a positive feature in its imaginary component at 3100 cm(-1).

Neuronal activity patterns in the mediodorsal thalamus and related cognitive circuits are modulated by metabotropic glutamate receptors

PubMed Central

Copeland, C.S.; Neale, S.A.; Salt, T.E.

2015-01-01

The mediodorsal thalamus (MD) likely plays an important role in cognition as it receives abundant afferent connections from the amygdala and prefrontal cortex (PFC). Indeed, disturbed activity within the MD is thought to precipitate cognitive deficits associated with schizophrenia. As compounds acting at the Group II metabotropic glutamate (mGlu) receptors (subtypes mGlu2/mGlu3) have efficacy in animal models of schizophrenia, we investigated whether a Group II agonist and an mGlu2 positive allosteric modulator (PAM) could modulate MD activity. Extracellular single-unit recordings were made in vivo from MD neurones in anaesthetised rats. Responses were elicited by electrical stimulation of the PFC and/or amygdala, with Group II compounds locally applied as required. The Group II agonist reduced inhibition evoked in the MD: an effect manifested as an increase in short-latency responses, and a decrease in long-latency burst-firing. This disinhibitory action of the Group II receptors in the MD represents a mechanism of potential therapeutic importance as increased inhibition in the MD has been associated with cognitive deficit-onset. Furthermore, as co-application of the mGlu2 PAM did not potentiate the Group II agonist effects in the MD, we suggest that the Group II disinhibitory effect is majority-mediated via mGlu3. This heterogeneity in Group II receptor thalamic physiology bears consequence, as compounds active exclusively at the mGlu2 subtype are unlikely to perturb maladapted MD firing patterns associated with cognitive deficits, with activity at mGlu3 receptors possibly more appropriate. Indeed, polymorphisms in the mGlu3, but not the mGlu2, gene have been detected in patients with schizophrenia. PMID:25576798

Bone mineral density and mammographic density in Mexican women

PubMed Central

Moseson, Heidi; Rice, Megan S.; López-Ridaura, Ruy; Bertrand, Kimberly A.; Torres, Gabriela; Blanco, Margarita; Tamayo-Orozco, Juan Alfredo; Lajous, Martin; Romieu, Isabelle

2016-01-01

Background Bone mineral density (BMD) is a putative marker for lifetime exposure to estrogen. Studies that have explored whether BMD is a determinant of mammographic density (MD) have observed inconsistent results. Therefore, we examined this potential association in a sample of women (N=1,516) from the clinical sub-cohort in the Mexican Teachers’ Cohort (N=115,315). Methods We used multivariable linear regression to assess the association between quartiles of BMD and percent MD, as well as total dense and non-dense area of the breast, stratified by menopausal status. We also examined the associations by body mass index (BMI) (<30kg/m2,, ≥30kg/m2). Results Overall, there was no association between BMD and MD among premenopausal women. However, when we stratified by BMI, there was a modest inverse association between BMD and percent MD (difference between extreme quartiles= −2.8, 95%CI: −5.9, 0.27, p-trend=0.04) among women with BMI <30 kg/m2, but a positive association among obese women (comparable difference=5.1, 95%CI: 0.02, 10.1, p-trend=0.03; p-interaction<0.01). Among postmenopausal women, BMD and percent MD were positively associated after adjustment for BMI (p-trend<0.01). Postmenopausal women in the highest two quartiles of BMD had 4–5 percentage point higher percent MD compared to women in the lowest quartile. The association did not differ by BMI in postmenopausal women (p-interaction=0.76). Conclusion Among obese premenopausal women as well as postmenopausal women, BMD was positively associated with percent MD. Among leaner premenopausal women, BMD and percent MD were modestly inversely associated. These findings support the hypothesis that cumulative exposure to estrogen (as measured by BMD) may influence MD. PMID:26463740

Antinociceptive synergism of MD-354 and clonidine. Part II. The alpha-adrenoceptor component.

PubMed

Young, Shawquia; Vainio, Minna; Scheinin, Mika; Dukat, Małgorzata

2010-08-01

Previously, we reported that antinociceptive synergism of a 5-HT(3)/alpha(2)-adrenoceptor ligand MD-354 (m-chlorophenylguanidine) and clonidine combination occurs, in part, through a 5-HT(3) receptor antagonist mechanism. In the present investigation, a possible role for alpha(2)-adrenoceptors was examined. Mechanistic studies using yohimbine (a subtype non-selective alpha(2)-adrenoceptor antagonist), BRL 44408 (a preferential alpha(2A)-adrenoceptor antagonist) and imiloxan (a preferential alpha(2B/C)-adrenoceptor antagonist) on the antinociceptive actions of a MD-354/clonidine combination were conducted. Subcutaneous pre-treatment with all three antagonists inhibited the antinociceptive synergism of MD-354 and clonidine in the mouse tail-flick assay in a dose-dependent manner (AD(50) = 0.33, 2.1, and 0.17 mg/kg, respectively). Enhancement of clonidine antinociception by MD-354 did not potentiate clonidine's locomotor suppressant activity in a mouse locomotor assay. When [ethyl-3H]RS-79948-197 was used as radioligand, MD-354 displayed almost equal affinity to alpha(2A)- and alpha(2B)-adrenoceptors (K(i) = 110 and 220 nM) and showed lower affinity at alpha(2C)-adrenoceptors (K(i) = 4,700 nM). MD-354 had no subtype-selectivity for the alpha(2)-adrenoceptor subtypes as an antagonist in functional [35S]GTPgammaS binding assays. MD-354 was a weak partial agonist at alpha(2A)-adrenoceptors. Overall, in addition to the 5-HT(3) receptor component, the present investigation found MD-354 to be a weak partial alpha(2A)-adrenoceptor agonist that enhances clonidine's thermal antinociceptive actions through an alpha(2)-adrenoceptor-mediated mechanism without augmenting sedation.

Comparison of Mammographic Density Assessed as Volumes and Areas among Women Undergoing Diagnostic Image-Guided Breast Biopsy

PubMed Central

Gierach, Gretchen L.; Geller, Berta M.; Shepherd, John A.; Patel, Deesha A.; Vacek, Pamela M.; Weaver, Donald L.; Chicoine, Rachael E.; Pfeiffer, Ruth M.; Fan, Bo; Mahmoudzadeh, Amir Pasha; Wang, Jeff; Johnson, Jason M.; Herschorn, Sally D.; Brinton, Louise A.; Sherman, Mark E.

2014-01-01

Background Mammographic density (MD), the area of non-fatty appearing tissue divided by total breast area, is a strong breast cancer risk factor. Most MD analyses have employed visual categorizations or computer-assisted quantification, which ignore breast thickness. We explored MD volume and area, using a volumetric approach previously validated as predictive of breast cancer risk, in relation to risk factors among women undergoing breast biopsy. Methods Among 413 primarily white women, ages 40–65, undergoing diagnostic breast biopsies between 2007–2010 at an academic facility in Vermont, MD volume (cm3) was quantified in cranio-caudal views of the breast contralateral to the biopsy target using a density phantom, while MD area (cm2) was measured on the same digital mammograms using thresholding software. Risk factor associations with continuous MD measurements were evaluated using linear regression. Results Percent MD volume and area were correlated (r=0.81) and strongly and inversely associated with age, body mass index (BMI), and menopause. Both measures were inversely associated with smoking and positively associated with breast biopsy history. Absolute MD measures were correlated (r=0.46) and inversely related to age and menopause. Whereas absolute dense area was inversely associated with BMI, absolute dense volume was positively associated. Conclusions Volume and area MD measures exhibit some overlap in risk factor associations, but divergence as well, particularly for BMI. Impact Findings suggest that volume and area density measures differ in subsets of women; notably, among obese women, absolute density was higher with volumetric methods, suggesting that breast cancer risk assessments may vary for these techniques. PMID:25139935

Do Chinese Children With Math Difficulties Have a Deficit in Executive Functioning?

PubMed Central

Wang, Xiaochen; Georgiou, George K.; Li, Qing; Tavouktsoglou, Athanasios

2018-01-01

Several studies have shown that Executive Functioning (EF) is a unique predictor of mathematics performance. However, whether or not children with mathematics difficulties (MD) experience deficits in EF remains unclear. Thus, the purpose of this study was to examine if Chinese children with MD experience deficits in EF. We assessed 23 children with MD (9 girls, mean age = 10.40 years), 30 children with reading difficulties and MD (RDMD; 12 girls, mean age = 10.82 years), and 31 typically-developing (TD) peers (16 girls, mean age = 10.41 years) on measures of inhibition (Color-Word Stroop, Inhibition), shifting of attention (Planned Connections, Rapid Alternating Stimuli), working memory (Digit Span Backwards, Listening Span), processing speed (Visual Matching, Planned Search), reading (Character Recognition, Sentence Verification), and mathematics (Addition and Subtraction Fluency, Math Standard Achievement Test). The results of MANOVA analyses showed first that the performance of the MD children in all EF tasks was worse than their TD peers. Second, with the exception of the shifting tasks in which the MD children performed better than the RDMD children, the performance of the two groups was similar in all measures of working memory and inhibition. Finally, covarying for the effects of processing speed eliminated almost all differences between the TD and MD groups (the only exception was Listening Span) as well as the differences between the MD and RDMD groups in shifting of attention. Taken together, our findings suggest that although Chinese children with MD (with or without comorbid reading difficulties) experience significant deficits in all EF skills, most of their deficits can be accounted by lower-level deficits in processing speed. PMID:29928246

Algorithms of GPU-enabled reactive force field (ReaxFF) molecular dynamics.

PubMed

Zheng, Mo; Li, Xiaoxia; Guo, Li

2013-04-01

Reactive force field (ReaxFF), a recent and novel bond order potential, allows for reactive molecular dynamics (ReaxFF MD) simulations for modeling larger and more complex molecular systems involving chemical reactions when compared with computation intensive quantum mechanical methods. However, ReaxFF MD can be approximately 10-50 times slower than classical MD due to its explicit modeling of bond forming and breaking, the dynamic charge equilibration at each time-step, and its one order smaller time-step than the classical MD, all of which pose significant computational challenges in simulation capability to reach spatio-temporal scales of nanometers and nanoseconds. The very recent advances of graphics processing unit (GPU) provide not only highly favorable performance for GPU enabled MD programs compared with CPU implementations but also an opportunity to manage with the computing power and memory demanding nature imposed on computer hardware by ReaxFF MD. In this paper, we present the algorithms of GMD-Reax, the first GPU enabled ReaxFF MD program with significantly improved performance surpassing CPU implementations on desktop workstations. The performance of GMD-Reax has been benchmarked on a PC equipped with a NVIDIA C2050 GPU for coal pyrolysis simulation systems with atoms ranging from 1378 to 27,283. GMD-Reax achieved speedups as high as 12 times faster than Duin et al.'s FORTRAN codes in Lammps on 8 CPU cores and 6 times faster than the Lammps' C codes based on PuReMD in terms of the simulation time per time-step averaged over 100 steps. GMD-Reax could be used as a new and efficient computational tool for exploiting very complex molecular reactions via ReaxFF MD simulation on desktop workstations. Copyright © 2013 Elsevier Inc. All rights reserved.

Does psychosis increase the risk of suicide in patients with major depression? A systematic review.

PubMed

Zalpuri, Isheeta; Rothschild, Anthony J

2016-07-01

Over the years studies have shown conflicting results about the risk of suicide in psychotic depression (MD-psych). To understand this association, we undertook a comprehensive review of the literature to ascertain whether individuals with MD-psych have higher rates of completed suicides, suicide attempts or suicidal ideation compared to those with non-psychotic depression (MD-nonpsych). We searched Pubmed, PsycINFO and Ovid in English language, from 1946-October 2015. Studies were included if suicidal ideation, attempts or completed suicides were assessed. During the acute episode of depression, patients with MD-psych have higher rates of suicide, suicide attempts, and suicidal ideation than patients with MD-nonpsych, especially when the patient is hospitalized on an inpatient psychiatric unit. Studies done after the acute episode has resolved are less likely to show this difference, likely due to patients having received treatment. Diagnostic interviews were not conducted in all studies. Many studies did not report whether psychotic symptoms in MD-psych patients were mood-congruent or mood-incongruent; hence it is unclear whether the type of delusion increases suicide risk. Studies did not describe whether MD-psych patients experienced command hallucinations encouraging them to engage in suicidal behavior. Only 24 studies met inclusion criteria; several of them had small sample size and a quality score of zero, hence impacting validity. This review indicates that the seemingly conflicting data in suicide risk between MD-psych and MD-nonpsych in previous studies appears to be related to whether one looks at differences during the acute episode or over the long-term. Copyright © 2016 Elsevier B.V. All rights reserved.

Structural insights into pharmacophore-assisted in silico identification of protein-protein interaction inhibitors for inhibition of human toll-like receptor 4 - myeloid differentiation factor-2 (hTLR4-MD-2) complex.

PubMed

Mishra, Vinita; Pathak, Chandramani

2018-05-29

Toll-like receptor 4 (TLR4) is a member of Toll-Like Receptors (TLRs) family that serves as a receptor for bacterial lipopolysaccharide (LPS). TLR4 alone cannot recognize LPS without aid of co-receptor myeloid differentiation factor-2 (MD-2). Binding of LPS with TLR4 forms a LPS-TLR4-MD-2 complex and directs downstream signaling for activation of immune response, inflammation and NF-κB activation. Activation of TLR4 signaling is associated with various pathophysiological consequences. Therefore, targeting protein-protein interaction (PPI) in TLR4-MD-2 complex formation could be an attractive therapeutic approach for targeting inflammatory disorders. The aim of present study was directed to identify small molecule PPI inhibitors (SMPPIIs) using pharmacophore mapping-based approach of computational drug discovery. Here, we had retrieved the information about the hot spot residues and their pharmacophoric features at both primary (TLR4-MD-2) and dimerization (MD-2-TLR4*) protein-protein interaction interfaces in TLR4-MD-2 homo-dimer complex using in silico methods. Promising candidates were identified after virtual screening, which may restrict TLR4-MD-2 protein-protein interaction. In silico off-target profiling over the virtually screened compounds revealed other possible molecular targets. Two of the virtually screened compounds (C11 and C15) were predicted to have an inhibitory concentration in μM range after HYDE assessment. Molecular dynamics simulation study performed for these two compounds in complex with target protein confirms the stability of the complex. After virtual high throughput screening we found selective hTLR4-MD-2 inhibitors, which may have therapeutic potential to target chronic inflammatory diseases.

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

Yin, L. H., E-mail: lhyin@issp.ac.cn, E-mail: ypsun@issp.ac.cn; Yang, J.; Dai, J. M.

We have investigated the detailed magnetic, magnetoelectric (ME), magnetodielectric (MD) and thermal expansion properties in Co{sub 4}Nb{sub 2}O{sub 9} crystal. A magnetic-field-induced spin flop was observed below antiferromagnetic (AFM) transition temperature T{sub N}. Dielectric constant at applied magnetic field nearly diverges around the AFM transition, giving rise to a colossal MD effect as high as ∼138% around T{sub N}. Theoretical analysis of the ME and MD data revealed a major contribution of critical spin fluctuation to the colossal MD effect in Co{sub 4}Nb{sub 2}O{sub 9}. These results suggest that linear ME materials with large ME coupling might be potentially usedmore » to realize large MD effect for future application.« less

Gaussian Accelerated Molecular Dynamics: Unconstrained Enhanced Sampling and Free Energy Calculation.

PubMed

Miao, Yinglong; Feher, Victoria A; McCammon, J Andrew

2015-08-11

A Gaussian accelerated molecular dynamics (GaMD) approach for simultaneous enhanced sampling and free energy calculation of biomolecules is presented. By constructing a boost potential that follows Gaussian distribution, accurate reweighting of the GaMD simulations is achieved using cumulant expansion to the second order. Here, GaMD is demonstrated on three biomolecular model systems: alanine dipeptide, chignolin folding, and ligand binding to the T4-lysozyme. Without the need to set predefined reaction coordinates, GaMD enables unconstrained enhanced sampling of these biomolecules. Furthermore, the free energy profiles obtained from reweighting of the GaMD simulations allow us to identify distinct low-energy states of the biomolecules and characterize the protein-folding and ligand-binding pathways quantitatively.

Gaussian Accelerated Molecular Dynamics: Unconstrained Enhanced Sampling and Free Energy Calculation

PubMed Central

2016-01-01

A Gaussian accelerated molecular dynamics (GaMD) approach for simultaneous enhanced sampling and free energy calculation of biomolecules is presented. By constructing a boost potential that follows Gaussian distribution, accurate reweighting of the GaMD simulations is achieved using cumulant expansion to the second order. Here, GaMD is demonstrated on three biomolecular model systems: alanine dipeptide, chignolin folding, and ligand binding to the T4-lysozyme. Without the need to set predefined reaction coordinates, GaMD enables unconstrained enhanced sampling of these biomolecules. Furthermore, the free energy profiles obtained from reweighting of the GaMD simulations allow us to identify distinct low-energy states of the biomolecules and characterize the protein-folding and ligand-binding pathways quantitatively. PMID:26300708

Multiple Simulated Annealing-Molecular Dynamics (MSA-MD) for Conformational Space Search of Peptide and Miniprotein

PubMed Central

Hao, Ge-Fei; Xu, Wei-Fang; Yang, Sheng-Gang; Yang, Guang-Fu

2015-01-01

Protein and peptide structure predictions are of paramount importance for understanding their functions, as well as the interactions with other molecules. However, the use of molecular simulation techniques to directly predict the peptide structure from the primary amino acid sequence is always hindered by the rough topology of the conformational space and the limited simulation time scale. We developed here a new strategy, named Multiple Simulated Annealing-Molecular Dynamics (MSA-MD) to identify the native states of a peptide and miniprotein. A cluster of near native structures could be obtained by using the MSA-MD method, which turned out to be significantly more efficient in reaching the native structure compared to continuous MD and conventional SA-MD simulation. PMID:26492886

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MD Simulations of P-Type ATPases in a Lipid Bilayer System.

PubMed

Autzen, Henriette Elisabeth; Musgaard, Maria

2016-01-01

Molecular dynamics (MD) simulation is a computational method which provides insight on protein dynamics with high resolution in both space and time, in contrast to many experimental techniques. MD simulations can be used as a stand-alone method to study P-type ATPases as well as a complementary method aiding experimental studies. In particular, MD simulations have proved valuable in generating and confirming hypotheses relating to the structure and function of P-type ATPases. In the following, we describe a detailed practical procedure on how to set up and run a MD simulation of a P-type ATPase embedded in a lipid bilayer using software free of use for academics. We emphasize general considerations and problems typically encountered when setting up simulations. While full coverage of all possible procedures is beyond the scope of this chapter, we have chosen to illustrate the MD procedure with the Nanoscale Molecular Dynamics (NAMD) and the Visual Molecular Dynamics (VMD) software suites.

Center of excellence for mobile sensor data-to-knowledge (MD2K).

PubMed

Kumar, Santosh; Abowd, Gregory D; Abraham, William T; al'Absi, Mustafa; Beck, J Gayle; Chau, Duen Horng; Condie, Tyson; Conroy, David E; Ertin, Emre; Estrin, Deborah; Ganesan, Deepak; Lam, Cho; Marlin, Benjamin; Marsh, Clay B; Murphy, Susan A; Nahum-Shani, Inbal; Patrick, Kevin; Rehg, James M; Sharmin, Moushumi; Shetty, Vivek; Sim, Ida; Spring, Bonnie; Srivastava, Mani; Wetter, David W

2015-11-01

Mobile sensor data-to-knowledge (MD2K) was chosen as one of 11 Big Data Centers of Excellence by the National Institutes of Health, as part of its Big Data-to-Knowledge initiative. MD2K is developing innovative tools to streamline the collection, integration, management, visualization, analysis, and interpretation of health data generated by mobile and wearable sensors. The goal of the big data solutions being developed by MD2K is to reliably quantify physical, biological, behavioral, social, and environmental factors that contribute to health and disease risk. The research conducted by MD2K is targeted at improving health through early detection of adverse health events and by facilitating prevention. MD2K will make its tools, software, and training materials widely available and will also organize workshops and seminars to encourage their use by researchers and clinicians. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Clinical investigation of the lesions responsible for sensory disturbance in Minamata disease.

PubMed

Uchino, M; Mita, S; Satoh, H; Hirano, T; Arimura, K; Nakagawa, M; Nakamura, M; Uyama, E; Ando, Y; Wakamiya, J; Futatsuka, M

2001-11-01

To clarify the lesions responsible for sensory disturbance in Minamata disease (MD), we clinically investigated the characteristics of sensory disturbance. In all patients with the classical type MD, two-point discrimination was severely disturbed, but the involvement of superficial sensation was relatively mild. On short-latency somatosensory evoked potential study, the component corresponding to N20 was completely absent with normal N9, N11, and N13 components. Although 14 of 38 chronic MD patients demonstrated intact superficial sensation, 10 of these 14 showed mild to moderate disturbance in two-point discrimination. The two-point discrimination in chronic MD patients was significantly high irrespective of the disturbance of superficial sensation. These findings suggest that the sensory disturbance of MD patients may mainly be caused by a lesion in the sensory cortex rather than in the peripheral nerves. However, other foci could be also responsible for the sensory impairment, since 9 of 38 chronic MD patients showed intact two-point discrimination.

Efficiency in nonequilibrium molecular dynamics Monte Carlo simulations

DOE PAGES

Radak, Brian K.; Roux, Benoît

2016-10-07

Hybrid algorithms combining nonequilibrium molecular dynamics and Monte Carlo (neMD/MC) offer a powerful avenue for improving the sampling efficiency of computer simulations of complex systems. These neMD/MC algorithms are also increasingly finding use in applications where conventional approaches are impractical, such as constant-pH simulations with explicit solvent. However, selecting an optimal nonequilibrium protocol for maximum efficiency often represents a non-trivial challenge. This work evaluates the efficiency of a broad class of neMD/MC algorithms and protocols within the theoretical framework of linear response theory. The approximations are validated against constant pH-MD simulations and shown to provide accurate predictions of neMD/MC performance.more » An assessment of a large set of protocols confirms (both theoretically and empirically) that a linear work protocol gives the best neMD/MC performance. Lastly, a well-defined criterion for optimizing the time parameters of the protocol is proposed and demonstrated with an adaptive algorithm that improves the performance on-the-fly with minimal cost.« less

The Hugoniot adiabat of crystalline copper based on molecular dynamics simulation and semiempirical equation of state

NASA Astrophysics Data System (ADS)

Gubin, S. A.; Maklashova, I. V.; Mel'nikov, I. N.

2018-01-01

The molecular dynamics (MD) method was used for prediction of properties of copper under shock-wave compression and clarification of the melting region of crystal copper. The embedded atom potential was used for the interatomic interaction. Parameters of Hugonoit adiabats of solid and liquid phases of copper calculated by the semiempirical Grüneisen equation of state are consistent with the results of MD simulations and experimental data. MD simulation allows to visualize the structure of cooper on the atomistic level. The analysis of the radial distribution function and the standard deviation by MD modeling allows to predict the melting area behind the shock wave front. These MD simulation data are required to verify the wide-range equation of state of metals. The melting parameters of copper based on MD simulations and semiempirical equations of state are consistent with experimental and theoretical data, including the region of the melting point of copper.

The effect of exercise training on clinical outcomes in patients with the metabolic syndrome: a systematic review and meta-analysis.

PubMed

Ostman, C; Smart, N A; Morcos, D; Duller, A; Ridley, W; Jewiss, D

2017-08-30

Purpose: to establish if exercise training improves clinical outcomes in people with metabolic syndrome (MetS). Registered with PROSPERO international prospective register of systematic reviews ( https://www.crd.york.ac.uk/PROSPERO/Identifier:CRD42017055491 ). studies were identified through a MEDLINE search strategy (1985 to Jan 12, 2017), Cochrane controlled trials registry, CINAHL and SPORTDiscus. prospective randomized or controlled trials of exercise training in humans with metabolic syndrome, lasting 12 weeks or more. We included 16 studies with 23 intervention groups; 77,000 patient-hours of exercise training. In analyses of aerobic exercise studies versus control: body mass index was significantly reduced, mean difference (MD) -0.29 (kg m -2 ) (95% CI -0.44, -0.15, p < 0.0001); body mass was significantly reduced, MD -1.16 kg (95% CI -1.83, -0.48, p = 0.0008); waist circumference was significantly reduced MD -1.37 cm (95% CI -2.02, -0.71, p < 0.0001), peak VO 2 was significantly improved MD 3.00 mL kg -1  min -1 (95% CI 1.92, 4.08, p < 0.000001); systolic blood pressure and diastolic blood pressure were significantly reduced, MD -2.54 mmHg (95% CI -4.34, -0.75, p = 0.006), and, MD -2.27 mmHg (95% CI -3.47, -1.06, p = 0.0002) respectively; fasting blood glucose was significantly reduced MD -0.16 mmol L -1 (95% CI -0.32, -0.01, p = 0.04); triglycerides were significantly reduced MD -0.21 mmol L -1 (95% CI -0.29, -0.13, p < 0.00001); and low density lipoprotein was significantly reduced MD -0.03 mmol L -1 (95% CI -0.05, -0.00, p = 0.02). In analyses of combined exercise versus control: waist circumference, MD -3.80 cm (95% CI -5.65, -1.95, p < 0.0001); peak VO 2 MD 4.64 mL kg -1  min -1 (95% CI 2.42, 6.87, p < 0.0001); systolic blood pressure MD -3.79 mmHg (95% CI -6.18, -1.40, p = 0.002); and high density lipoprotein (HDL) MD 0.14 (95% CI 0.04, 0.25, p = 0.009) were all significantly improved. We found no significant differences between outcome measures between the two exercise interventions. Exercise training improves body composition, cardiovascular, and, metabolic outcomes in people with metabolic syndrome. For some outcome measures, isolated aerobic exercise appears optimal.

A dsRNA-binding protein MdDRB1 associated with miRNA biogenesis modifies adventitious rooting and tree architecture in apple.

PubMed

You, Chun-Xiang; Zhao, Qiang; Wang, Xiao-Fei; Xie, Xing-Bin; Feng, Xiao-Ming; Zhao, Ling-Ling; Shu, Huai-Rui; Hao, Yu-Jin

2014-02-01

Although numerous miRNAs have been already isolated from fruit trees, knowledge about miRNA biogenesis is largely unknown in fruit trees. Double-strand RNA-binding (DRB) protein plays an important role in miRNA processing and maturation; however, its role in the regulation of economically important traits is not clear yet in fruit trees. EST blast and RACE amplification were performed to isolate apple MdDRB1 gene. Following expression analysis, RNA binding and protein interaction assays, MdDRB1 was transformed into apple callus and in vitro tissue cultures to characterize the functions of MdDRB1 in miRNA biogenesis, adventitious rooting, leaf development and tree growth habit. MdDRB1 contained two highly conserved DRB domains. Its transcripts existed in all tissues tested and are induced by hormones. It bound to double-strand RNAs and interacted with AtDCL1 (Dicer-Like 1) and MdDCL1. Chip assay indicated its role in miRNA biogenesis. Transgenic analysis showed that MdDRB1 controls adventitious rooting, leaf curvature and tree architecture by modulating the accumulation of miRNAs and the transcript levels of miRNA target genes. Our results demonstrated that MdDRB1 functions in the miRNA biogenesis in a conserved way and that it is a master regulator in the formation of economically important traits in fruit trees. © 2013 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

A comparison between elastic network interpolation and MD simulation of 16S ribosomal RNA.

PubMed

Kim, Moon K; Li, Wen; Shapiro, Bruce A; Chirikjian, Gregory S

2003-12-01

In this paper a coarse-grained method called elastic network interpolation (ENI) is used to generate feasible transition pathways between two given conformations of the core central domain of 16S Ribosomal RNA (16S rRNA). The two given conformations are the extremes generated by a molecular dynamics (MD) simulation, which differ from each other by 10A in root-mean-square deviation (RMSD). It takes only several hours to build an ENI pathway on a 1.5GHz Pentium with 512 MB memory, while the MD takes several weeks on high-performance multi-processor servers such as the SGI ORIGIN 2000/2100. It is shown that multiple ENI pathways capture the essential anharmonic motions of millions of timesteps in a particular MD simulation. A coarse-grained normal mode analysis (NMA) is performed on each intermediate ENI conformation, and the lowest 1% of the normal modes (representing about 40 degrees of freedom (DOF)) are used to parameterize fluctuations. This combined ENI/NMA method captures all intermediate conformations in the MD run with 1.5A RMSD on average. In addition, if we restrict attention to the time interval of the MD run between the two extreme conformations, the RMSD between the closest ENI/NMA pathway and the MD results is about 1A. These results may serve as a paradigm for reduced-DOF dynamic simulations of large biological macromolecules as well as a method for the reduced-parameter interpretation of massive amounts of MD data.

Development of thalamocortical connections between the mediodorsal thalamus and the prefrontal cortex and its implication in cognition

PubMed Central

Ferguson, Brielle R.; Gao, Wen-Jun

2015-01-01

The mediodorsal thalamus (MD) represents a fundamental subcortical relay to the prefrontal cortex (PFC), and is thought to be highly implicated in modulation of cognitive performance. Additionally, it undergoes highly conserved developmental stages, which, when dysregulated, can have detrimental consequences. Embryonically, the MD experiences a tremendous surge in neurogenesis and differentiation, and disruption of this process may underlie the pathology in certain neurodevelopmental disorders. However, during the postnatal period, a vast amount of cell loss in the MD occurs. These together may represent an extended critical period for postnatal development, in which disturbances in the normal growth or reduction of the MD afferents to the PFC, can result in PFC-dependent cognitive, affective, or psychotic abnormalities. In this review, we explore the current knowledge supporting this hypothesis of a protracted critical period, and propose how developmental changes in the MD contribute to successful prefrontal cortical development and function. Specifically, we elaborate on the unique properties of MD-PFC connections compared with other thalamocortical afferents in sensory cortices, examine how MD-PFC innervation modulates synaptic transmission in the local prefrontal circuitry, and speculate on what occurs during postnatal development, particularly within the early neonatal stage, as well as juvenile and adolescent periods. Finally, we discuss the questions that remain and propose future experiments in order to provide perspective and novel insights into the cause of neuropsychiatric disorders associated with MD-PFC development. PMID:25620923

Vestibular evoked myogenic potentials (VEMP) can detect asymptomatic saccular hydrops.

PubMed

Lin, Ming-Yee; Timmer, Ferdinand C A; Oriel, Brad S; Zhou, Guangwei; Guinan, John J; Kujawa, Sharon G; Herrmann, Barbara S; Merchant, Saumil N; Rauch, Steven D

2006-06-01

The objective of this study was to explore the useful of vestibular evoked myogenic potential (VEMP) testing for detecting endolymphatic hydrops, especially in the second ear of patients with unilateral Ménière disease (MD). This study was performed at a tertiary care academic medical center. Part I consisted of postmortem temporal bone specimens from the temporal bone collection of the Massachusetts Eye & Ear Infirmary; part II consisted of consecutive consenting adult patients (n = 82) with unilateral MD by American Academy of Otolaryngology-Head and Neck Surgery criteria case histories. Outcome measures consisted of VEMP thresholds in patients and histologic saccular endolymphatic hydrops in postmortem temporal bones. Saccular hydrops was observed in the asymptomatic ear in six of 17 (35%) of temporal bones from donors with unilateral MD. Clinic patients with unilateral MD showed elevated mean VEMP thresholds and altered VEMP tuning in their symptomatic ears and, to a lesser degree, in their asymptomatic ears. Specific VEMP frequency and tuning criteria were used to define a "Ménière-like" response. This "Ménière-like" response was seen in 27% of asymptomatic ears of our patients with unilateral MD. Bilateral involvement is seen in approximately one third of MD cases. Saccular hydrops appears to precede symptoms in bilateral MD. Changes in VEMP threshold and tuning appear to be sensitive to these structural changes in the saccule. If so, then VEMP may be useful as a detector of asymptomatic saccular hydrops and as a predictor of evolving bilateral MD.

Breast cancer: a global perspective.

PubMed

Collyar, D E

2001-09-15

The 2001 American Society of Clinical Oncology (ASCO) International Symposium, Breast Cancer: A Global Perspective, was conducted by members of the ASCO International Committee and additional speakers from around the world. An interactive format was chosen to: (1) learn how patterns of incidence, epidemiology, and causal biology relate to breast cancer around the world; (2) discuss the challenges in screening, diagnosis, and treatment of breast cancer, as well as its socioeconomic impact in various regions; (3) describe international differences in approach to and management of advanced breast cancer; and (4) discuss treatment in terms of hormone response, clinical research, and drug metabolism. After a brief introduction, each speaker gave an overview of breast cancer challenges and issues in their country, and discussed how the following case might be diagnosed and treated: A 44-year-old mother who presents with a finding of a painless breast lump and no prior history of breast masses, trauma, or surgery. Comments from a patient perspective were then presented, followed by a panel discussion and closing remarks. Co-chairs of this Symposium included Deborah Collyar (President, PAIR-Patient Advocates in Research) and Elizabeth Eisenhauer, MD (Director, Investigational New Drug Program, National Cancer Institute of Canada Clinical Trials Group). Speakers included Gilberto Schwartsmann, MD (South America), Monica Morrow, MD (North America), Daniel Vorobiof, MD (South Africa), Rakesh Chopra, MD (India), Klaus Hoeffken, MD (Eastern Europe), Russell Basser, MD (Australia), Susan Matsuko Shinigawa (patient perspective), and Larry Norton, MD (closing remarks).

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY 2018 POSITION STATEMENT ON INTEGRATION OF INSULIN PUMPS AND CONTINUOUS GLUCOSE MONITORING IN PATIENTS WITH DIABETES MELLITUS.

PubMed

Grunberger, George; Handelsman, Yehuda; Bloomgarden, Zachary T; Fonseca, Vivian A; Garber, Alan J; Haas, Richard A; Roberts, Victor L; Umpierrez, Guillermo E

2018-03-01

This document represents the official position of the American Association of Clinical Endocrinologists and American College of Endocrinology. Where there are no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician. AACE/ACE Task Force on Integration of Insulin Pumps and Continuous Glucose Monitoring in the Management of Patients With Diabetes Mellitus Chair George Grunberger, MD, FACP, FACE Task Force Members Yehuda Handelsman, MD, FACP, FNLA, MACE Zachary T. Bloomgarden, MD, MACE Vivian A. Fonseca, MD, FACE Alan J. Garber, MD, PhD, FACE Richard A. Haas, MD, FACE Victor L. Roberts, MD, MBA, FACP, FACE Guillermo E. Umpierrez, MD, CDE, FACP, FACE Abbreviations: AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology A1C = glycated hemoglobin BGM = blood glucose monitoring CGM = continuous glucose monitoring CSII = continuous subcutaneous insulin infusion DM = diabetes mellitus FDA = Food & Drug Administration MDI = multiple daily injections T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus SAP = sensor-augmented pump SMBG = self-monitoring of blood glucose STAR 3 = Sensor-Augmented Pump Therapy for A1C Reduction phase 3 trial.

Intestinal permeability and Ménière's disease.

PubMed

Di Berardino, F; Zanetti, D; Ciusani, E; Caccia, C; Leoni, V; De Grazia, U; Filipponi, E; Elli, L

Ménière disease (MD) is a multifactorial chronic disabling condition characterized by episodic vertigo, ear fullness, and hearing loss. MD patients often complain of aspecific gastrointestinal symptoms associated with autonomic dysregulation, frequently outweighed by the otological manifestations. Dietary modifications have been reported to improve the typical MD symptoms in some cases. Our purpose was to test the urinary levels of lactulose and mannitol (double sugar test) and the fecal calprotectin, both markers of altered intestinal permeability, in subjects with definite MD in an active and inactive stage. Twenty-six with definite unilateral MD were studied: 14 patients were symptomatic for at least 3months with moderate to severe vertigo spells and a functional level ≥4; 12 patients had been asymptomatic (no vertigo spells) for at least 3months and had a functional level=1 at the time of testing. Twenty healthy volunteers were recruited as "control group". Lactulose and mannitol absorption was significantly increased in the symptomatic M patients compared to the asymptomatic group (p<0.02 and p<0.004, respectively) and to the controls. FC were also higher than normal only in the symptomatic group. (p<0.01). An altered intestinal permeability, according to the two assays, was found only in symptomatic MD patients. The rationale for a possible relationship between MD and intestinal permeability is forwarded. The double-sugar test and FC quantification might be implemented in the MD diagnostic workup. Copyright © 2017 Elsevier Inc. All rights reserved.

Online distribution channel increases article usage on Mendeley: a randomized controlled trial.

PubMed

Kudlow, Paul; Cockerill, Matthew; Toccalino, Danielle; Dziadyk, Devin Bissky; Rutledge, Alan; Shachak, Aviv; McIntyre, Roger S; Ravindran, Arun; Eysenbach, Gunther

2017-01-01

Prior research shows that article reader counts (i.e. saves) on the online reference manager, Mendeley, correlate to future citations. There are currently no evidenced-based distribution strategies that have been shown to increase article saves on Mendeley. We conducted a 4-week randomized controlled trial to examine how promotion of article links in a novel online cross-publisher distribution channel (TrendMD) affect article saves on Mendeley. Four hundred articles published in the Journal of Medical Internet Research were randomized to either the TrendMD arm ( n  = 200) or the control arm ( n  = 200) of the study. Our primary outcome compares the 4-week mean Mendeley saves of articles randomized to TrendMD versus control. Articles randomized to TrendMD showed a 77% increase in article saves on Mendeley relative to control. The difference in mean Mendeley saves for TrendMD articles versus control was 2.7, 95% CI (2.63, 2.77), and statistically significant ( p  < 0.01). There was a positive correlation between pageviews driven by TrendMD and article saves on Mendeley (Spearman's rho r  = 0.60). This is the first randomized controlled trial to show how an online cross-publisher distribution channel (TrendMD) enhances article saves on Mendeley. While replication and further study are needed, these data suggest that cross-publisher article recommendations via TrendMD may enhance citations of scholarly articles.

Which Instructional Practices Most Help First Grade Students with and without Mathematics Difficulties?

PubMed Central

Morgan, Paul L.; Farkas, George; Maczuga, Steve

2015-01-01

We used population-based, longitudinal data to investigate the relation between mathematics instructional practices used by 1st grade teachers in the U.S. and the mathematics achievement of their students. Factor analysis identified four types of instructional activities (i.e., teacher-directed, student-centered, manipulatives/calculators, movement/music) and eight types of specific skills taught (e.g., adding two-digit numbers). First-grade students were then classified into five groups on the basis of their fall and/or spring of kindergarten mathematics achievement—three groups with mathematics difficulties (MD) and two without MD. Regression analysis indicated that a higher percentage of MD students in 1st grade classrooms was associated with greater use by teachers of manipulatives/calculators and movement/music to teach mathematics. Yet follow-up analysis for each of the MD and non-MD groups indicated that only teacher-directed instruction was significantly associated with the achievement of students with MD (covariate-adjusted ESs = .05–.07). The largest predicted effect for a specific instructional practice was for routine practice and drill. In contrast, for both groups of non-MD students, teacher-directed and student-centered instruction had approximately equal, statistically significant positive predicted effects (covariate-adjusted ESs = .03–.04). First-grade teachers in the U.S. may need to increase their use of teacher-directed instruction if they are to raise the mathematics achievement of students with MD. PMID:26180268

Maternal role development: the impact of maternal distress and social support following childbirth.

PubMed

Emmanuel, Elizabeth N; Creedy, Debra K; St John, Winsome; Brown, Claire

2011-04-01

to explore the relationship between maternal role development (MRD), maternal distress (MD) and social support following childbirth. prospective longitudinal survey. three public hospital maternity units in Brisbane, Australia. 630 pregnant women were invited to participate in the study, with a 77% (n=473) completion rate. to measure MRD, the Prenatal Maternal Expectation Scale was used at 36 weeks of pregnancy, and the revised What Being the Parent of a New Baby is Like (with subscales of evaluation, centrality and life change) was used at six and 12 weeks post partum. At all three data collection points, the Edinburgh Postnatal Depression Scale was used to measure MD, and the Maternal Social Support Scale was used to measure social support. at 36 weeks of gestation, optimal scaling for MRD produced a parsimonious model with MD providing 39% of predictive power. At six weeks post partum, similar models predicting MRD were found (evaluation: r(2)=0.14, MD providing 64% of predictive power; centrality: r(2)=0.07, MD providing 11% of predictive power; life change: r(2)=0.26, MD providing 59% of predictive power). At 12 weeks post partum, MD was a predictor for evaluation (r(2)=0.11) and life change (r(2)=0.26, 54% of predictive power). there is a statistically significant but moderate correlation between MRD and MD. The transition to motherhood can be stressful, but may be facilitated by appropriate acknowledgement and support with an emphasis on MRD. Copyright © 2009 Elsevier Ltd. All rights reserved.

Molecular Genetic Analysis of an Endotoxin Nonresponder Mutant Cell Line

PubMed Central

Schromm, Andra B.; Lien, Egil; Henneke, Philipp; Chow, Jesse C.; Yoshimura, Atsutoshi; Heine, Holger; Latz, Eicke; Monks, Brian G.; Schwartz, David A.; Miyake, Kensuke; Golenbock, Douglas T.

2001-01-01

Somatic cell mutagenesis is a powerful tool for characterizing receptor systems. We reported previously two complementation groups of mutant cell lines derived from CD14-transfected Chinese hamster ovary–K1 fibroblasts defective in responses to bacterial endotoxin. Both classes of mutants expressed a normal gene product for Toll-like receptor (TLR)4, and fully responded to stimulation by tumor necrosis factor (TNF)-α or interleukin (IL)-1β. We identified the lesion in one of the complementation groups in the gene for MD-2, a putative TLR4 coreceptor. The nonresponder phenotype of this mutant was reversed by transfection with MD-2. Cloning of MD-2 from the nonresponder cell line revealed a point mutation in a highly conserved region resulting in a C95Y amino acid exchange. Both forms of MD-2 colocalized with TLR4 on the cell surface after transfection, but only the wild-type cDNA reverted the lipopolysaccharide (LPS) nonresponder phenotype. Furthermore, soluble MD-2, but not soluble MD-2C95Y, functioned to enable LPS responses in cells that expressed TLR4. Thus, MD-2 is a required component of the LPS signaling complex and can function as a soluble receptor for cells that do not otherwise express it. We hypothesize that MD-2 conformationally affects the extracellular domain of TLR4, perhaps resulting in a change in affinity for LPS or functioning as a portion of the true ligand for TLR4. PMID:11435474

Sex, stressful life events, and adult onset depression and alcohol dependence: are men and women equally vulnerable?

PubMed

Slopen, Natalie; Williams, David R; Fitzmaurice, Garrett M; Gilman, Stephen E

2011-08-01

Higher rates of major depression (MD) among females, and of alcohol dependence (AD) among males, are among the most routinely reported findings in psychiatric epidemiology. One of the most often pursued explanations for sex differences in both disorders suggests that males and females have a differential vulnerability to stressors, which is manifested in sex-specific ways (MD for females, AD for males). However, existing evidence in support of this explanation is mixed. In the present study, we investigated sex differences in the association between stressful life events and MD and AD in a large national sample of adults in the United States (n = 32,744) using a prospective design. Logistic regression was used to estimate associations between stressful life events and both MD and AD; sex-specific effects of stress on MD and AD were evaluated by testing interaction terms between sex and stressors in the prediction of both outcomes. The number of stressful life events was predictive of first onset MD and AD. This was true for both males and females, and sex-by-stress interaction terms did not support the hypothesis that sex-specific responses to stressful life events lead to sex differences in first onset of MD and AD among adults. These results indicate the resistance of sex differences in MD and AD to simple explanations, and suggest the need for more nuanced models that incorporate both physiological and social aspects of vulnerability. Copyright © 2011 Elsevier Ltd. All rights reserved.

Reducing phosphorus loss in tile water with managed drainage in a claypan soil.

PubMed

Nash, Patrick R; Nelson, Kelly A; Motavalli, Peter P; Nathan, Manjula; Dudenhoeffer, Chris

2015-03-01

Installing subsurface tile drain systems in poorly drained claypan soils to improve corn ( L.) yields could potentially increase environmental phosphorus (P) loss through the tile drainage system. The objectives of the study were to quantify the average concentration and loss of ortho-P in tile drain water from a claypan soil and to determine whether managed subsurface drainage (MD) could reduce ortho-P loss in tile water compared with free subsurface drainage (FD). Flow-weighted ortho-P concentration in the tile water was significantly lower with MD (0.09 mg L) compared with that of FD (0.15 mg L). Ortho-P loss in the tile water of this study was reduced with MD (36 g ha) by 80% compared with FD (180 g ha). Contrary to previous research, reduced ortho-P loss observed over the 4-yr study was not solely due to the reduced amount of water drained annually (63%) with MD compared with FD. During the spring period, when flow was similar between MD and FD, the concentration of ortho-P in the tile water generally was lower with MD compared with FD, which resulted in significantly less ortho-P loss with MD. We speculate that MD's ability to conserve water during the dry summer months increased corn's uptake of water and P, which reduced the amount of P available for leaching loss in the subsequent springs. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

The repeatability of mean defect with size III and size V standard automated perimetry.

PubMed

Wall, Michael; Doyle, Carrie K; Zamba, K D; Artes, Paul; Johnson, Chris A

2013-02-15

The mean defect (MD) of the visual field is a global statistical index used to monitor overall visual field change over time. Our goal was to investigate the relationship of MD and its variability for two clinically used strategies (Swedish Interactive Threshold Algorithm [SITA] standard size III and full threshold size V) in glaucoma patients and controls. We tested one eye, at random, for 46 glaucoma patients and 28 ocularly healthy subjects with Humphrey program 24-2 SITA standard for size III and full threshold for size V each five times over a 5-week period. The standard deviation of MD was regressed against the MD for the five repeated tests, and quantile regression was used to show the relationship of variability and MD. A Wilcoxon test was used to compare the standard deviations of the two testing methods following quantile regression. Both types of regression analysis showed increasing variability with increasing visual field damage. Quantile regression showed modestly smaller MD confidence limits. There was a 15% decrease in SD with size V in glaucoma patients (P = 0.10) and a 12% decrease in ocularly healthy subjects (P = 0.08). The repeatability of size V MD appears to be slightly better than size III SITA testing. When using MD to determine visual field progression, a change of 1.5 to 4 decibels (dB) is needed to be outside the normal 95% confidence limits, depending on the size of the stimulus and the amount of visual field damage.

78 FR 11896 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-20

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PDA Cell Substrate Task Force: Emerging Technologies for Virus Detection Technical Document--A Progress Report.

PubMed

King, Kathryn; Wiebe, Michael

2011-01-01

CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA).

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Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-17

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33 CFR 110.71a - Cabin Creek, Grasonville, Md.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Cabin Creek, Grasonville, Md. 110.71a Section 110.71a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71a Cabin Creek, Grasonville, Md. The waters...

33 CFR 110.72 - Blackhole Creek, Md.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Blackhole Creek, Md. 110.72 Section 110.72 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.72 Blackhole Creek, Md. The waters on the west side of...

33 CFR 110.71a - Cabin Creek, Grasonville, Md.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Cabin Creek, Grasonville, Md. 110.71a Section 110.71a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71a Cabin Creek, Grasonville, Md. The waters...

33 CFR 110.71a - Cabin Creek, Grasonville, Md.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Cabin Creek, Grasonville, Md. 110.71a Section 110.71a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71a Cabin Creek, Grasonville, Md. The waters...

33 CFR 110.71a - Cabin Creek, Grasonville, Md.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Cabin Creek, Grasonville, Md. 110.71a Section 110.71a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71a Cabin Creek, Grasonville, Md. The waters...

33 CFR 110.71a - Cabin Creek, Grasonville, Md.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Cabin Creek, Grasonville, Md. 110.71a Section 110.71a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71a Cabin Creek, Grasonville, Md. The waters...

33 CFR 110.72 - Blackhole Creek, Md.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Blackhole Creek, Md. 110.72 Section 110.72 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.72 Blackhole Creek, Md. The waters on the west side of...

Muscle Dysmorphia: A New Form of Eating Disorder?

ERIC Educational Resources Information Center

Goodale, Kimberly R.; Watkins, Patti Lou; Cardinal, Bradley J.

2001-01-01

Examined symptoms of muscle dysmorphia (MD), a variation of the eating disorders anorexia nervosa and bulimia, among college students. Surveys indicated that MD symptomatology appears in the general population and among both sexes. MD significantly related to eating disorder pathology and depression, and to some degree to impaired social support.…

76 FR 66075 - Center for Scientific Review Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-25

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Fractions Learning in Children with Mathematics Difficulties

ERIC Educational Resources Information Center

Tian, Jing; Siegler, Robert S.

2017-01-01

Learning fractions is difficult for children in general and especially difficult for children with mathematics difficulties (MD). Recent research on developmental and individual differences in fraction knowledge of children with MD and typically achieving (TA) children has demonstrated that U.S. children with MD start middle school behind their TA…

Fractions Learning in Children with Mathematics Difficulties

ERIC Educational Resources Information Center

Tian, Jing; Siegler, Robert S.

2016-01-01

Learning of fractions is difficult for children in general and especially difficult for children with mathematics difficulties (MD). Recent research on developmental and individual differences in fraction knowledge of MD and typically achieving (TA) children has demonstrated that U.S. children with MD start middle school behind TA peers in…

State Code Guides | Efficient Windows Collaborative

Science.gov Websites

CO-2012 Connecticut CT-2018 CT-2015 CT-2012 Delaware DE-2018 DE-2015 DE-2012 District of Columbia DC LA-2018 LA-2015 LA-2012 Maine ME-2018 ME-2015 ME-2012 Maryland MD-2018 MD-2015 MD-2012 Massachusetts

77 FR 66623 - National Institute on Minority Health and Health Disparities; Notice of Closed Meeting

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2012-11-06

... and Health Disparities Special Emphasis Panel; NIMHD Community-Based Participatory Research (CBPR... Marriott Suites, 6711 Democracy Boulevard, Bethesda, MD 20817. Contact Person: Robert Nettey, M.D., Chief... of Health, 6707 Democracy Blvd., Suite 800, Bethesda, MD 20892, (301) 496-3996, [email protected

Genome-wide histone modification profile induced by MDV in MD-resistant and -susceptible chickens

USDA-ARS?s Scientific Manuscript database

Marek’s disease (MD) is a lymphoproliferative disease in chicken caused by oncogenic Marek’s disease virus (MDV). MD is characterized by infiltration of proliferating lymphoid cells in organs, such as peripheral nerve, skin, muscle, liver, spleen, heart, kidney, gonads and proventriculus. Epigenetic...

Math Disabilities: A Selective Meta-Analysis of the Literature

ERIC Educational Resources Information Center

Swanson, H. Lee; Jerman, Olga

2006-01-01

This article synthesizes published literature comparing the cognitive functioning of children who have math disabilities (MD) with that of (a) average-achieving children; (b) children who have reading disabilities (RD); and (c) children who have co-morbid disabilities (MD+RD). Average achievers outperformed children with MD on measures of verbal…

Time Estimation Deficits in Childhood Mathematics Difficulties

ERIC Educational Resources Information Center

Hurks, Petra P. M.; van Loosbroek, Erik

2014-01-01

Time perception has not been comprehensively examined in mathematics difficulties (MD). Therefore, verbal time estimation, production, and reproduction were tested in 13 individuals with MD and 16 healthy controls, matched for age, sex, and intellectual skills. Individuals with MD performed comparably to controls in time reproduction, but showed a…

75 FR 9421 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

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2010-03-02

... Neuroscience Center, 6001 Executive Boulevard, Rockville, MD 20852 (Telephone Conference Call). Contact Person... Research, NINDS/NIH/DHHS/Neuroscience Center, 6001 Executive Boulevard, Suite 3204, MSC 9529, Bethesda, MD.../Neuroscience Center, 6001 Executive Boulevard, Suite 3204, MSC 9529, Bethesda, MD 20892, (301) 496-0660...

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2012-02-17

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78 FR 66027 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

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2013-11-04

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2011-09-30

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2013-02-25

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2011-04-11

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2012-06-20

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Report of the NIH Panel to Define Principles of Therapy of HIV Infection and Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents. Vol. 47/No. RR-5.

DTIC Science & Technology

1998-04-25

MA David Cooper, M.D. National Center for HIV Epidemiology and Clinical Research Sydney, NSW, Australia Stephen Follansbee, M.D. Davies...National Association of People with AIDS Washington, DC David Barr, J.D. Forum for Collaborative HIV Research Washington, DC Samuel Bozzette, M.D...Mellors, M.D. University of Pittsburgh Pittsburgh, PA David Nash, M.D. Thomas Jefferson University Philadelphia, PA Sallie Perryman New York

Multidimensional Recurrence Quantification Analysis (MdRQA) for the Analysis of Multidimensional Time-Series: A Software Implementation in MATLAB and Its Application to Group-Level Data in Joint Action

PubMed Central

Wallot, Sebastian; Roepstorff, Andreas; Mønster, Dan

2016-01-01

We introduce Multidimensional Recurrence Quantification Analysis (MdRQA) as a tool to analyze multidimensional time-series data. We show how MdRQA can be used to capture the dynamics of high-dimensional signals, and how MdRQA can be used to assess coupling between two or more variables. In particular, we describe applications of the method in research on joint and collective action, as it provides a coherent analysis framework to systematically investigate dynamics at different group levels—from individual dynamics, to dyadic dynamics, up to global group-level of arbitrary size. The Appendix in Supplementary Material contains a software implementation in MATLAB to calculate MdRQA measures. PMID:27920748

Multidimensional Recurrence Quantification Analysis (MdRQA) for the Analysis of Multidimensional Time-Series: A Software Implementation in MATLAB and Its Application to Group-Level Data in Joint Action.

PubMed

Wallot, Sebastian; Roepstorff, Andreas; Mønster, Dan

2016-01-01

We introduce Multidimensional Recurrence Quantification Analysis (MdRQA) as a tool to analyze multidimensional time-series data. We show how MdRQA can be used to capture the dynamics of high-dimensional signals, and how MdRQA can be used to assess coupling between two or more variables. In particular, we describe applications of the method in research on joint and collective action, as it provides a coherent analysis framework to systematically investigate dynamics at different group levels-from individual dynamics, to dyadic dynamics, up to global group-level of arbitrary size. The Appendix in Supplementary Material contains a software implementation in MATLAB to calculate MdRQA measures.

[Relationship between anthropometric variables and muscle dysmorphia in gymnasts in the province of Alicante].

PubMed

Martínez Segura, Asier; Rizo Baeza, María Mercedes; Sánchez Ferrer, Marina; Reig García-Galbis, Manuel; Cortés Castell, Ernesto

2014-11-01

It shows a new study that examines if the anthropometric measurements can be used to classify the muscle dysmorphia (MD), in gymnasts who attend fitness room. Gymnasts were analyzed several weights rooms of Alicante (urban area of southeastern Spain), where the measurements were 141 males aged between 18-45 years, aiming to enhance their muscle mass. We had in mind the calculation of BMI (kg/m2), the somatotype (endomorphy, mesomorphy and ectomorphy) and have been classified potential cases of muscle dysmorphia, using the Muscle appareance satisfaction escale. The sample was composed of 68 normoweight; 66 overweight and 7 obese, classified as MD in a 25.0% the normoweight, 33.3% overweight and 85.7% of the obese (p=0.004 ). On the somatotype, the only component that presents differences between non-MD and MD is mesomorphy (p=0.024). Muscle dysmorphia is a concept clearly difficult psychological diagnosable using anthropometric measures. Mesomorphy is the only measure that is increased in the MD, and may be a parameter to aid in the diagnosis and follow-up to the MD. In addition, the risk of developing MD is increase with the degree of obesity. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Microsatellite markers associated with resistance to Marek's disease in commercial layer chickens.

PubMed

McElroy, J P; Dekkers, J C M; Fulton, J E; O'Sullivan, N P; Soller, M; Lipkin, E; Zhang, W; Koehler, K J; Lamont, S J; Cheng, H H

2005-11-01

The objective of the current study was to identify QTL conferring resistance to Marek's disease (MD) in commercial layer chickens. To generate the resource population, 2 partially inbred lines that differed in MD-caused mortality were intermated to produce 5 backcross families. Vaccinated chicks were challenged with very virulent plus (vv+) MD virus strain 648A at 6 d and monitored for MD symptoms. A recent field isolate of the MD virus was used because the lines were resistant to commonly used older laboratory strains. Selective genotyping was employed using 81 microsatellites selected based on prior results with selective DNA pooling. Linear regression and Cox proportional hazard models were used to detect associations between marker genotypes and survival. Significance thresholds were validated by simulation. Seven and 6 markers were significant based on proportion of false positive and false discovery rate thresholds less than 0.2, respectively. Seventeen markers were associated with MD survival considering a comparison-wise error rate of 0.10, which is about twice the number expected by chance, indicating that at least some of the associations represent true effects. Thus, the present study shows that loci affecting MD resistance can be mapped in commercial layer lines. More comprehensive studies are under way to confirm and extend these results.

Accelerated Molecular Dynamics Simulations with the AMOEBA Polarizable Force Field on Graphics Processing Units

PubMed Central

2013-01-01

The accelerated molecular dynamics (aMD) method has recently been shown to enhance the sampling of biomolecules in molecular dynamics (MD) simulations, often by several orders of magnitude. Here, we describe an implementation of the aMD method for the OpenMM application layer that takes full advantage of graphics processing units (GPUs) computing. The aMD method is shown to work in combination with the AMOEBA polarizable force field (AMOEBA-aMD), allowing the simulation of long time-scale events with a polarizable force field. Benchmarks are provided to show that the AMOEBA-aMD method is efficiently implemented and produces accurate results in its standard parametrization. For the BPTI protein, we demonstrate that the protein structure described with AMOEBA remains stable even on the extended time scales accessed at high levels of accelerations. For the DNA repair metalloenzyme endonuclease IV, we show that the use of the AMOEBA force field is a significant improvement over fixed charged models for describing the enzyme active-site. The new AMOEBA-aMD method is publicly available (http://wiki.simtk.org/openmm/VirtualRepository) and promises to be interesting for studying complex systems that can benefit from both the use of a polarizable force field and enhanced sampling. PMID:24634618

A Mediterranean Diet Model in Australia: Strategies for Translating the Traditional Mediterranean Diet into a Multicultural Setting

PubMed Central

Kucianski, Teagan; Moschonis, George; Tierney, Audrey C.; Itsiopoulos, Catherine

2018-01-01

Substantial evidence supports the effect of the Mediterranean Diet (MD) for managing chronic diseases, although trials have been primarily conducted in Mediterranean populations. The efficacy and feasibility of the Mediterranean dietary pattern for the management of chronic diseases has not been extensively evaluated in non-Mediterranean settings. This paper aims to describe the development of a MD model that complies with principles of the traditional MD applied in a multiethnic context. Optimal macronutrient and food-based composition was defined, and a two-week menu was devised incorporating traditional ingredients with evidence based on improvements in chronic disease management. Strategies were developed for the implementation of the diet model in a multiethnic population. Consistent with the principles of a traditional MD, the MD model was plant-based and high in dietary fat, predominantly monounsaturated fatty acids from extra virgin olive oil. Fruits, vegetables and wholegrains were a mainstay, and moderate amounts of nuts and seeds, fish, dairy and red wine were recommended. The diet encompassed key features of the MD including cuisine, biodiversity and sustainability. The MD model preserved traditional dietary components likely to elicit health benefits for individuals with chronic diseases, even with the adaptation to an Australian multiethnic population. PMID:29642557

The Multiple-Demand System in the Novelty of Musical Improvisation: Evidence from an MRI Study on Composers.

PubMed

Lu, Jing; Yang, Hua; He, Hui; Jeon, Seun; Hou, Changyue; Evans, Alan C; Yao, Dezhong

2017-01-01

The multiple-demand (MD) system has proven to be associated with creating structured mental programs in comprehensive behaviors, but the functional mechanisms of this system have not been clarified in the musical domain. In this study, we explored the hypothesis that the MD system is involved in a comprehensive music-related behavior known as musical improvisation. Under a functional magnetic resonance imaging (fMRI) paradigm, 29 composers were recruited to improvise melodies through visual imagery tasks according to familiar and unfamiliar cues. We found that the main regions of the MD system were significantly activated during both musical improvisation conditions. However, only a greater involvement of the intraparietal sulcus (IPS) within the MD system was shown when improvising with unfamiliar cues. Our results revealed that the MD system strongly participated in musical improvisation through processing the novelty of melodies, working memory, and attention. In particular, improvising with unfamiliar cues required more musical transposition manipulations. Moreover, both functional and structural analyses indicated evidence of neuroplasticity in MD regions that could be associated with musical improvisation training. These findings can help unveil the functional mechanisms of the MD system in musical cognition, as well as improve our understanding of musical improvisation.

The Multiple-Demand System in the Novelty of Musical Improvisation: Evidence from an MRI Study on Composers

PubMed Central

Lu, Jing; Yang, Hua; He, Hui; Jeon, Seun; Hou, Changyue; Evans, Alan C.; Yao, Dezhong

2017-01-01

The multiple-demand (MD) system has proven to be associated with creating structured mental programs in comprehensive behaviors, but the functional mechanisms of this system have not been clarified in the musical domain. In this study, we explored the hypothesis that the MD system is involved in a comprehensive music-related behavior known as musical improvisation. Under a functional magnetic resonance imaging (fMRI) paradigm, 29 composers were recruited to improvise melodies through visual imagery tasks according to familiar and unfamiliar cues. We found that the main regions of the MD system were significantly activated during both musical improvisation conditions. However, only a greater involvement of the intraparietal sulcus (IPS) within the MD system was shown when improvising with unfamiliar cues. Our results revealed that the MD system strongly participated in musical improvisation through processing the novelty of melodies, working memory, and attention. In particular, improvising with unfamiliar cues required more musical transposition manipulations. Moreover, both functional and structural analyses indicated evidence of neuroplasticity in MD regions that could be associated with musical improvisation training. These findings can help unveil the functional mechanisms of the MD system in musical cognition, as well as improve our understanding of musical improvisation. PMID:29311776

Separation and preparation of 6-gingerol from molecular distillation residue of Yunnan ginger rhizomes by high-speed counter-current chromatography and the antioxidant activity of ginger oils in vitro.

PubMed

Gan, Zhilin; Liang, Zheng; Chen, Xiaosong; Wen, Xin; Wang, Yuxiao; Li, Mo; Ni, Yuanying

2016-02-01

Molecular distillation residue (MD-R) from ginger had the most total phenol content of 247.6mg gallic acid equivalents per gram (GAE/g) among the ginger oils. High-speed counter-current chromatography (HSCCC) technique in semi-preparative scale was successfully performed in separation and purification of 6-gingerol from MD-R by using a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (10:2:5:7, v/v/v/v). The target compound was isolated, collected, purified by HSCCC in the head-tail mode, and then analyzed by HPLC. A total of 90.38±0.53mg 6-gingerol was obtained from 600mg MD-R, with purity of 99.6%. In addition, the structural identification of 6-gingerol was performed by EI/MS, (1)H NMR and (13)C NMR. Moreover, the orders of antioxidant activity were vitamin E (VE)>supercritical fluid extraction oleoresin (SFE-O)=MD-R=6-gingerol>molecular distillation essential oil (MD-EO) and butylated hydroxytoluene (BHT)=VE>6-gingerol>MD-R=SFE-O>MD-EO, respectively in 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging and β-Carotene bleaching. Copyright © 2016 Elsevier B.V. All rights reserved.

Fouling and long-term durability of an integrated forward osmosis and membrane distillation system.

PubMed

Husnain, T; Mi, B; Riffat, R

2015-01-01

An integrated forward osmosis (FO) and membrane distillation (MD) system has great potential for sustainable wastewater reuse. However, the fouling and long-term durability of the system remains largely unknown. This study investigates the fouling behaviour and efficiency of cleaning procedures of FO and MD membranes used for treating domestic wastewater. Results showed that a significant decline in flux of both FO and MD membranes were observed during treatment of wastewater with organic foulants. However, shear force generated by the increased cross-flow physically removed the loosely attached foulants from the FO membrane surface and resulted in 86-88% recovery of flux by cleaning with tap water. For the MD membrane, almost no flux recovery was achieved due to adsorption of organic foulants on the hydrophobic membrane surface, thus indicating significant irreversible fouling/wetting, which may not be effectively cleaned even with chemical reagents. Long-term (10 d) tests showed consistent performance of the FO membrane by rejecting the contaminants. However, organic foulants reduced the hydrophobicity of the MD membrane, caused wetting problems and allowed contaminants to pass through. The results demonstrate that combination of the FO and MD processes can effectively reduce irreversible membrane fouling and solve the wetting problem of the MD membrane.

Moisture-Mediated Interactions Between Amorphous Maltodextrins and Crystalline Fructose.

PubMed

Thorat, Alpana; Marrs, Krystin N; Ghorab, Mohamed K; Meunier, Vincent; Forny, Laurent; Taylor, Lynne S; Mauer, Lisa J

2017-05-01

The effects of coformulating amorphous maltodextrins (MDs) and crystalline fructose, a deliquescent solid, on the moisture sorption, deliquescence point (RH 0 ), and glass transition temperature (T g ) behaviors were determined. Moisture sorption profiles of binary fructose:MD mixtures and individual ingredients were generated using controlled relative humidity (RH) desiccators and by dynamic vapor sorption techniques. Blends exhibited synergistic moisture uptake at RHs below the RH 0 of fructose, attributed to partial dissolution of fructose in plasticized MD matrices without a significant reduction in the RH 0 of the undissolved fructose. Increasing storage temperature decreased the onset RH for moisture sorption synergy. At all storage RHs, the measured T g (2nd scan) was significantly reduced in fructose:MD mixtures compared to individual MDs, and was related to both the synergistic moisture uptake in the blends and heat-induced ternary fructose-MD-water interactions in the differential scanning calorimeter. Differences were found between the behavior of fructose:MD blends and previous reports of sucrose:MD and NaCl:MD blends, caused in part by the lower RH 0 of fructose. The enhanced moisture sorption in blends of deliquescent and amorphous ingredients could lead to problematic moisture-induced changes if storage conditions are not controlled. © 2017 Institute of Food Technologists®.

Proinflammatory cytokines and response to molds in mononuclear cells of patients with Meniere disease.

PubMed

Frejo, Lidia; Gallego-Martinez, Alvaro; Requena, Teresa; Martin-Sanz, Eduardo; Amor-Dorado, Juan Carlos; Soto-Varela, Andres; Santos-Perez, Sofia; Espinosa-Sanchez, Juan Manuel; Batuecas-Caletrio, Angel; Aran, Ismael; Fraile, Jesus; Rossi-Izquierdo, Marcos; Lopez-Escamez, Jose Antonio

2018-04-13

Epidemiological studies have found a higher prevalence of allergic symptoms and positive prick tests in patients with Meniere's disease (MD); however the effect of allergenic extracts in MD has not been established. Thus, this study aims to determine the effect of Aspergillus and Penicillium stimulation in cytokine release and gene expression profile in MD. Patients with MD showed higher basal levels of IL-1β, IL-1RA, IL-6 and TNF-α when compared to healthy controls. We observed that IL-1β levels had a bimodal distribution suggesting two different subgroups of patients, with low and high basal levels of cytokines. Gene expression profile in peripheral blood mononuclear cells (PBMC) showed significant differences in patients with high and low basal levels of IL-1β. We found that both mold extracts triggered a significant release of TNF-α in MD patients, which were not found in controls. Moreover, after mold stimulation, MD patients showed a different gene expression profile in PBMC, according to the basal levels of IL-1β. The results indicate that a subset of MD patients have higher basal levels of proinflammatory cytokines and the exposure to Aspergillus and Penicillium extracts may trigger additional TNF-α release and contribute to exacerbate inflammation.

QwikMD — Integrative Molecular Dynamics Toolkit for Novices and Experts

PubMed Central

Ribeiro, João V.; Bernardi, Rafael C.; Rudack, Till; Stone, John E.; Phillips, James C.; Freddolino, Peter L.; Schulten, Klaus

2016-01-01

The proper functioning of biomolecules in living cells requires them to assume particular structures and to undergo conformational changes. Both biomolecular structure and motion can be studied using a wide variety of techniques, but none offers the level of detail as do molecular dynamics (MD) simulations. Integrating two widely used modeling programs, namely NAMD and VMD, we have created a robust, user-friendly software, QwikMD, which enables novices and experts alike to address biomedically relevant questions, where often only molecular dynamics simulations can provide answers. Performing both simple and advanced MD simulations interactively, QwikMD automates as many steps as necessary for preparing, carrying out, and analyzing simulations while checking for common errors and enabling reproducibility. QwikMD meets also the needs of experts in the field, increasing the efficiency and quality of their work by carrying out tedious or repetitive tasks while enabling easy control of every step. Whether carrying out simulations within the live view mode on a small laptop or performing complex and large simulations on supercomputers or Cloud computers, QwikMD uses the same steps and user interface. QwikMD is freely available by download on group and personal computers. It is also available on the cloud at Amazon Web Services. PMID:27216779

A Mediterranean Diet Model in Australia: Strategies for Translating the Traditional Mediterranean Diet into a Multicultural Setting.

PubMed

George, Elena S; Kucianski, Teagan; Mayr, Hannah L; Moschonis, George; Tierney, Audrey C; Itsiopoulos, Catherine

2018-04-09

Substantial evidence supports the effect of the Mediterranean Diet (MD) for managing chronic diseases, although trials have been primarily conducted in Mediterranean populations. The efficacy and feasibility of the Mediterranean dietary pattern for the management of chronic diseases has not been extensively evaluated in non-Mediterranean settings. This paper aims to describe the development of a MD model that complies with principles of the traditional MD applied in a multiethnic context. Optimal macronutrient and food-based composition was defined, and a two-week menu was devised incorporating traditional ingredients with evidence based on improvements in chronic disease management. Strategies were developed for the implementation of the diet model in a multiethnic population. Consistent with the principles of a traditional MD, the MD model was plant-based and high in dietary fat, predominantly monounsaturated fatty acids from extra virgin olive oil. Fruits, vegetables and wholegrains were a mainstay, and moderate amounts of nuts and seeds, fish, dairy and red wine were recommended. The diet encompassed key features of the MD including cuisine, biodiversity and sustainability. The MD model preserved traditional dietary components likely to elicit health benefits for individuals with chronic diseases, even with the adaptation to an Australian multiethnic population.

QwikMD — Integrative Molecular Dynamics Toolkit for Novices and Experts

NASA Astrophysics Data System (ADS)

Ribeiro, João V.; Bernardi, Rafael C.; Rudack, Till; Stone, John E.; Phillips, James C.; Freddolino, Peter L.; Schulten, Klaus

2016-05-01

The proper functioning of biomolecules in living cells requires them to assume particular structures and to undergo conformational changes. Both biomolecular structure and motion can be studied using a wide variety of techniques, but none offers the level of detail as do molecular dynamics (MD) simulations. Integrating two widely used modeling programs, namely NAMD and VMD, we have created a robust, user-friendly software, QwikMD, which enables novices and experts alike to address biomedically relevant questions, where often only molecular dynamics simulations can provide answers. Performing both simple and advanced MD simulations interactively, QwikMD automates as many steps as necessary for preparing, carrying out, and analyzing simulations while checking for common errors and enabling reproducibility. QwikMD meets also the needs of experts in the field, increasing the efficiency and quality of their work by carrying out tedious or repetitive tasks while enabling easy control of every step. Whether carrying out simulations within the live view mode on a small laptop or performing complex and large simulations on supercomputers or Cloud computers, QwikMD uses the same steps and user interface. QwikMD is freely available by download on group and personal computers. It is also available on the cloud at Amazon Web Services.

MD-2 is required for disulfide HMGB1–dependent TLR4 signaling

PubMed Central

Wang, Haichao; Ju, Zhongliang; Ragab, Ahmed A.; Lundbäck, Peter; Long, Wei; Valdes-Ferrer, Sergio I.; He, Mingzhu; Pribis, John P.; Li, Jianhua; Lu, Ben; Gero, Domokos; Szabo, Csaba; Antoine, Daniel J.; Harris, Helena E.; Golenbock, Doug T.; Meng, Jianmin; Roth, Jesse; Chavan, Sangeeta S.; Andersson, Ulf; Billiar, Timothy R.; Al-Abed, Yousef

2015-01-01

Innate immune receptors for pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) orchestrate inflammatory responses to infection and injury. Secreted by activated immune cells or passively released by damaged cells, HMGB1 is subjected to redox modification that distinctly influences its extracellular functions. Previously, it was unknown how the TLR4 signalosome distinguished between HMGB1 isoforms. Here we demonstrate that the extracellular TLR4 adaptor, myeloid differentiation factor 2 (MD-2), binds specifically to the cytokine-inducing disulfide isoform of HMGB1, to the exclusion of other isoforms. Using MD-2–deficient mice, as well as MD-2 silencing in macrophages, we show a requirement for HMGB1-dependent TLR4 signaling. By screening HMGB1 peptide libraries, we identified a tetramer (FSSE, designated P5779) as a specific MD-2 antagonist preventing MD-2–HMGB1 interaction and TLR4 signaling. P5779 does not interfere with lipopolysaccharide-induced cytokine/chemokine production, thus preserving PAMP-mediated TLR4–MD-2 responses. Furthermore, P5779 can protect mice against hepatic ischemia/reperfusion injury, chemical toxicity, and sepsis. These findings reveal a novel mechanism by which innate systems selectively recognize specific HMGB1 isoforms. The results may direct toward strategies aimed at attenuating DAMP-mediated inflammation while preserving antimicrobial immune responsiveness. PMID:25559892

Ectopic expression of an apple cytochrome P450 gene MdCYPM1 negatively regulates plant photomorphogenesis and stress response in Arabidopsis.

PubMed

An, Jian-Ping; Li, Rui; Qu, Feng-Jia; You, Chun-Xiang; Wang, Xiao-Fei; Hao, Yu-Jin

2017-01-29

Cytochrome P450s play an important role in plant growth and are involved in multiple stresses response. However, little is known about the functions of cytochrome P450s in apple. Here, a Malus × domestica cytochrome P450 monooxygenase 1 gene, MdCYPM1, was identified and subsequently cloned from apple 'Gala' (Malus × domestica). To verify the functions of MdCYPM1, we generated transgenic Arabidopsis plants expressing the apple MdCYPM1 gene under the control of the Cauliflower mosaic virus 35S promoter. Four transgenic lines (#3, #5, #7 and #8) were selected for further study. The transgenic plants exhibited a series of skotomorphogenesis phenotypes relative to wild-type controls, such as reduction of the chlorophyll, anthocyanins content and hypocotyls elongation. In addition, overexpression of MdCYPM1 influenced auxin transport and flowering time in transgenic Arabidopsis. Furthermore, MdCYPM1 expression was induced by salt and mannitol treatments, and the transgenic plants were negatively regulated by salinity and osmotic stresses during germination. These results suggest that MdCYPM1 plays a vital role in plant growth and development. Copyright © 2017 Elsevier Inc. All rights reserved.

Probiotics, prebiotics infant formula use in preterm or low birth weight infants: a systematic review

PubMed Central

2012-01-01

Background Previous reviews (2005 to 2009) on preterm infants given probiotics or prebiotics with breast milk or mixed feeds focused on prevention of Necrotizing Enterocolitis, sepsis and diarrhea. This review assessed if probiotics, prebiotics led to improved growth and clinical outcomes in formula fed preterm infants. Methods Cochrane methodology was followed using randomized controlled trials (RCTs) which compared preterm formula containing probiotic(s) or prebiotic(s) to conventional preterm formula in preterm infants. The mean difference (MD) and corresponding 95% confidence intervals (CI) were reported for continuous outcomes, risk ratio (RR) and corresponding 95% CI for dichotomous outcomes. Heterogeneity was assessed by visual inspection of forest plots and a chi2 test. An I2 test assessed inconsistencies across studies. I2> 50% represented substantial heterogeneity. Results Four probiotics studies (N=212), 4 prebiotics studies (N=126) were included. Probiotics: There were no significant differences in weight gain (MD 1.96, 95% CI: -2.64 to 6.56, 2 studies, n=34) or in maximal enteral feed (MD 35.20, 95% CI: -7.61 to 78.02, 2 studies, n=34), number of stools per day increased significantly in probiotic group (MD 1.60, 95% CI: 1.20 to 2.00, 1 study, n=20). Prebiotics: Galacto-oligosaccharide / Fructo-oligosaccharide (GOS/FOS) yielded no significant difference in weight gain (MD 0.04, 95% CI: -2.65 to 2.73, 2 studies, n=50), GOS/FOS yielded no significant differences in length gain (MD 0.01, 95% CI: -0.03 to 0.04, 2 studies, n=50). There were no significant differences in head growth (MD −0.01, 95% CI: -0.02 to 0.00, 2 studies, n=76) or age at full enteral feed (MD −0.79, 95% CI: -2.20 to 0.61, 2 studies, n=86). Stool frequency increased significantly in prebiotic group (MD 0.80, 95% CI: 0.48 to 1.1, 2 studies, n=86). GOS/FOS and FOS yielded higher bifidobacteria counts in prebiotics group (MD 2.10, 95% CI: 0.96 to 3.24, n=27) and (MD 0.48, 95% CI: 0.28 to 0.68, n=56). Conclusions There is not enough evidence to state that supplementation with probiotics or prebiotics results in improved growth and clinical outcomes in exclusively formula fed preterm infants. PMID:22928998

Mammographic density and risk of breast cancer according to tumor characteristics and mode of detection: a Spanish population-based case-control study

PubMed Central

2013-01-01

Introduction It is not clear whether high mammographic density (MD) is equally associated with all subtypes of breast cancer (BC). We investigated the association between MD and subsequent BC, considering invasiveness, means of detection, pathologic subtype, and the time elapsed since mammographic exploration and BC diagnosis. Methods BC cases occurring in the population of women who attended screening from 1997 through 2004 in Navarre, a Spanish region with a fully consolidated screening program, were identified via record linkage with the Navarre Cancer Registry (n = 1,172). Information was extracted from the records of their first attendance at screening in that period. For each case, we randomly selected four controls, matched by screening round, year of birth, and place of residence. Cases were classified according to invasiveness (ductal carcinoma in situ (DCIS) versus invasive tumors), pathologic subtype (considering hormonal receptors and HER2), and type of diagnosis (screen-detected versus interval cases). MD was evaluated by a single, experienced radiologist by using a semiquantitative scale. Data on BC risk factors were obtained by the screening program in the corresponding round. The association between MD and tumor subtype was assessed by using conditional logistic regression. Results MD was clearly associated with subsequent BC. The odds ratio (OR) for the highest MD category (MD >75%) compared with the reference category (MD <10%) was similar for DCIS (OR = 3.47; 95% CI = 1.46 to 8.27) and invasive tumors (OR = 2.95; 95% CI = 2.01 to 4.35). The excess risk was particularly high for interval cases (OR = 7.72; 95% CI = 4.02 to 14.81) in comparison with screened detected tumors (OR = 2.17; 95% CI = 1.40 to 3.36). Sensitivity analyses excluding interval cases diagnosed in the first year after MD assessment or immediately after an early recall to screening yielded similar results. No differences were seen regarding pathologic subtypes. The excess risk associated with MD persisted for at least 7 to 8 years after mammographic exploration. Conclusions Our results confirm that MD is an important risk factor for all types of breast cancer. High breast density strongly increases the risk of developing an interval tumor, and this excess risk is not completely explained by a possible masking effect. PMID:23360535

Cardiac involvement in female Duchenne and Becker muscular dystrophy carriers in comparison to their first-degree male relatives: a comparative cardiovascular magnetic resonance study.

PubMed

Florian, Anca; Rösch, Sabine; Bietenbeck, Michael; Engelen, Markus; Stypmann, Jörg; Waltenberger, Johannes; Sechtem, Udo; Yilmaz, Ali

2016-03-01

Duchenne (DMD) and Becker (BMD) muscular dystrophies are X-linked recessive disorders associated with both skeletal myopathy and progressive cardiomyopathy in males. Female DMD/BMD carriers (DMDc/BMDc) are mostly free of skeletal muscle symptoms, but they are also prone to cardiomyopathy. The aim of the current study was to characterize the frequency, pattern, and extent of cardiomyopathy in female DMD/BMD carriers (DMDc/BMDc) in comparison to their first-degree male MD relatives. Thirty-six (age 44 ± 14 years) female MD carriers (20 DMDc and 16 BMDc) constituted the 'MD carrier group' and were prospectively enrolled. All MD carriers underwent a complete CMR study comprising cine- and late gadolinium enhancement (LGE) imaging. In 22 of these women ('female MD carrier comparison group', 7 DMD and 15 BMD), at least one first-degree male relative with a previously established diagnosis of MD underwent the same CMR protocol and was assigned to the 'male MD comparison group' (n = 24, 6 DMD and 18 BMD). In the total MD carrier group, 17 (47%) MD carriers had at least one pathological CMR finding [5 (14%) with a reduced left ventricular ejection fraction (LV-EF) and 16 (44%) with the presence of LGE]. All LGE-positive patients (n = 16) showed non-ischaemic LGE with subepicardial involvement of the LV lateral free wall being the most frequent pattern (13/16, 81%). Compared with BMDc, DMDc demonstrated more frequently a pathological CMR result (65 vs. 19%; P = 0.008)--in spite of being significantly younger (40 ± 11 vs. 50 ± 16 years, P = 0.038). In the male MD comparison group, the same LGE pattern as in female carriers was seen, but with a significantly higher prevalence of cardiac abnormalities compared with their female carrier relatives constituting the female MD comparison group (75 vs. 27%; P = 0.003). Cardiac involvement is a frequent finding in female carriers of DMD, but less frequently observed in carriers of BMD. Those DMDc and BMDc with cardiac involvement demonstrate the same myocardial fibrosis pattern as their male counterparts with overt disease. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Androgens for the anaemia of chronic kidney disease in adults.

PubMed

Yang, Qianchun; Abudou, Minawaer; Xie, Xi Sheng; Wu, Taixiang

2014-10-09

Anaemia occurs when blood contains fewer red blood cells and lower haemoglobin levels than normal, and is a common complication among adults with chronic kidney disease (CKD). Although a number of approaches are applied to correct anaemia in adults with CKD, the use of androgen therapy is controversial. The aim of this review was to determine the benefits and harms of androgens for the treatment of anaemia in adult patients with CKD. We searched CENTRAL, the Cochrane Renal Group's Specialised Register, the Chinese Biomedicine Database (CBM), CNKI, VIP and reference lists of articles without language restriction. The most recent search was conducted in August 2014. All randomised controlled trials (RCTs) that assessed the use of androgens for treating anaemia of CKD in adults were eligible for inclusion. Two authors independently extracted data and assessed risk of bias in the included studies. Meta-analyses were performed using relative risk (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). We included eight studies that reported data from 181 participants. Study quality was assessed as moderate in six studies, one was low quality, and one was high quality. The small number of included studies, and low participant numbers adversely influenced evidence quality overall.We found limited evidence (1 study, 24 participants) to indicate that oxymetholone can increase haemoglobin (Hb) (MD 1.90 g/dL, 95% CI 1.66 to 2.14), haematocrit (HCT) (MD 27.10%, 95% CI 26.49 to 27.71), change in albumin (MD 4.91 g/L, 95% CI 3.69 to 6.13), alanine aminotransferase (ALT) (MD 54.50 U/L, 95% CI 43.94 to 65.06), and aspartate aminotransferase (AST) (MD 47.33 U/L, 95% CI 37.69 to 56.97); and decrease high-density lipoprotein (HDL) (MD -15.66 mg/dL, 95% CI -24.84 to -6.48). We also found that compared with erythropoietin alone, nandrolone decanoate plus erythropoietin may increase HCT (3 studies, 73 participants: MD 2.54%, 95% Cl 0.96 to 4.12). Compared with erythropoietin (1 study, 27 participants), limited evidence was found to suggest that nandrolone decanoate can increase plasma total protein (MD 0.40 g/L, 95% CI 0.13 to 0.67), albumin (MD 0.20 g/L, 95% CI 0.01 to 0.39), and transferrin (MD 45.00 mg/dL, 95% CI 12.61 to 77.39) levels. Compared with no therapy (remnant kidney), evidence was found to suggest that nandrolone decanoate can increase Hb (2 studies, 33 participants: MD 1.04 g/dL, 95% Cl 0.66 to 1.41) and HCT (1 study, 24 participants: MD 3.70%, 95% Cl 0.68 to 6.72). Compared with no therapy (anephric), evidence was found (1 study, 5 participants) to suggest that nandrolone decanoate can increase Hb (MD 1.30 g/dL, 95% Cl 0.57 to 2.03), but nandrolone decanoate did not increase HCT (MD 2.00%, 95% Cl -0.85 to 4.85).However, oxymetholone was not found to reduce blood urea nitrogen (BUN), serum creatinine (SCr), cholesterol, or triglycerides; or increase plasma total protein, prealbumin, or transferrin. No evidence was found to indicate that nandrolone decanoate increased prealbumin or decreased BUN, SCr, AST, ALT, cholesterol, triglycerides, HDL or low-density lipoprotein (LDL). Adverse events associated with androgen therapy were reported infrequently. We found insufficient evidence to confirm that use of androgens for adults with CKD-related anaemia is beneficial.

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

Molecular Dynamics Simulations with Quantum Mechanics/Molecular Mechanics and Adaptive Neural Networks.

PubMed

Shen, Lin; Yang, Weitao

2018-03-13

Direct molecular dynamics (MD) simulation with ab initio quantum mechanical and molecular mechanical (QM/MM) methods is very powerful for studying the mechanism of chemical reactions in a complex environment but also very time-consuming. The computational cost of QM/MM calculations during MD simulations can be reduced significantly using semiempirical QM/MM methods with lower accuracy. To achieve higher accuracy at the ab initio QM/MM level, a correction on the existing semiempirical QM/MM model is an attractive idea. Recently, we reported a neural network (NN) method as QM/MM-NN to predict the potential energy difference between semiempirical and ab initio QM/MM approaches. The high-level results can be obtained using neural network based on semiempirical QM/MM MD simulations, but the lack of direct MD samplings at the ab initio QM/MM level is still a deficiency that limits the applications of QM/MM-NN. In the present paper, we developed a dynamic scheme of QM/MM-NN for direct MD simulations on the NN-predicted potential energy surface to approximate ab initio QM/MM MD. Since some configurations excluded from the database for NN training were encountered during simulations, which may cause some difficulties on MD samplings, an adaptive procedure inspired by the selection scheme reported by Behler [ Behler Int. J. Quantum Chem. 2015 , 115 , 1032 ; Behler Angew. Chem., Int. Ed. 2017 , 56 , 12828 ] was employed with some adaptions to update NN and carry out MD iteratively. We further applied the adaptive QM/MM-NN MD method to the free energy calculation and transition path optimization on chemical reactions in water. The results at the ab initio QM/MM level can be well reproduced using this method after 2-4 iteration cycles. The saving in computational cost is about 2 orders of magnitude. It demonstrates that the QM/MM-NN with direct MD simulations has great potentials not only for the calculation of thermodynamic properties but also for the characterization of reaction dynamics, which provides a useful tool to study chemical or biochemical systems in solution or enzymes.

Effects of persistent Mal de debarquement syndrome on balance, psychological traits, and motor cortex exctiability.

PubMed

Clark, Brian C; LePorte, Andrew; Clark, Shawn; Hoffman, Richard L; Quick, Adam; Wilson, Thad E; Thomas, James S

2013-03-01

Mal de debarquement syndrome (MdDS) is a poorly characterized and understood disorder of perceived motion. We sought to characterize postural control and the psychological impact of MdDS. Additionally, we explored whether patients with MdDS exhibit altered corticospinal and intracortical excitability. In a case-control study we compared patients with MdDS to age- and sex-matched controls (n=8/group). Postural stability (σr) was quantified from plane phase plots based on center or pressure, and psychological indices of depression, fatigue and kinesiophobia were obtained. Transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability by quantifying the motor evoked potential (MEP) amplitude of the flexor carpi radialis, and intracortical excitability was assessed by quantifying indices of intracortical facilitation (ICF), and short-interval and long-interval intracortical inhibition using a paired-pulse TMS paradigm. The patients with MdDS exhibited greater mean (±standard error of the mean) σr during semi-tandem stance (10.9 ± 1.5 compared to 7.1 ± 0.7, p=0.04), higher levels of kinesiophobia (41.6 ± 2.8 compared to 27.3 ± 2.2), and higher levels of fatigue (27.0 ± 4.1 compared to 48.4 ± 1.0). Patients with MdDS exhibited a higher mean motor threshold (MT) (58.1 ± 2.5 compared to 47.4 ± 2.7% of stimulator output), and larger MEP (13.1 ± 3.1 compared to 5.1 ± 1.2% of maximal compound muscle action potential) but there was no difference in measures of intracortical excitability. These findings suggest that patients with MdDS exhibit impaired postural stability, and high levels of kinesiophobia and fatigue. Additionally, we observed that patients with MdDS exhibit higher MT and large MEP amplitudes, but do not exhibit differences in measures of intracortical excitability, compared to controls. These findings help characterize MdDS, and provide insight into the physiology of MdDS. Copyright © 2012 Elsevier Ltd. All rights reserved.

Smoking Cessation Treatment for Patients With Mental Disorders Using CBT and Combined Pharmacotherapy.

PubMed

Loreto, Aline Rodrigues; Carvalho, Carlos Felipe Cavalcanti; Frallonardo, Fernanda Piotto; Ismael, Flavia; Andrade, Arthur Guerra de; Castaldelli-Maia, João Maurício

2017-01-01

The aim of this study was to investigate smoking treatment effectiveness and retention in a population with and without mental disorders (MD). Participants received cognitive behavioral therapy (CBT) plus nicotine patch alone or in combination with other medications (i.e., gum, bupropion, or nortriptyline) for smoking cessation treatment in a Brazilian Psychosocial Care Center unit (CAPS), taking into account sociodemographics and smoking profile covariates. The study involved comparison of treatment success (seven-day point prevalence abstinence at the end of the treatment) and retention (presence of the individual in all of the four medical consultations and six group sessions) in two subsamples of patients with MD (n = 267) and without MD (n = 397) who were included in a six-week treatment provided by a CAPS from 2007 to 2013. The treatment protocol comprised group CBT and pharmacotherapy (nicotine patches, nicotine gums, and bupropion and nortriptyline available, prescribed by psychiatrists). Within patients with MD, CBT plus nicotine patch plus bupropion (aOR = 2.00, 95% CI [1.14, 3.50], p = .015) and CBT plus nicotine patch plus gum (aOR = 2.10, 95% CI [1.04, 4.23], p = .036) were associated with treatment success. Within patients without MD, female gender (aOR = 0.60, 95% CI [0.37, 0.95], p = .031) and lower Heaviness of Smoking Index score (aOR = 0.80, 95% CI [0.65, 0.99], p = .048) were associated with treatment success. No variable was associated with dropout or retention within patients with or without MD. Our findings support the use of CBT plus nicotine patch plus bupropion as well as CBT plus nicotine patch plus gum in samples with high rates of medical, psychiatric, and addiction disorders. These findings support those of previous studies in the general population. Pharmacological treatment associated with group CBT based on cognitive-behavioral concepts and combined with ongoing MD treatment seems to be the best option for smoking cessation treatment among patients with MD. Units that deal with patients with MD, such as CAPS in Brazil, should be encouraged to treat smoking addiction in this population. Future studies should investigate retention rates in other samples of patients with MD.

Early Postnatal Lesion of the Medial Dorsal Nucleus Leads to Loss of Dendrites and Spines in Adult Prefrontal Cortex

PubMed Central

Marmolejo, Naydu; Paez, Jesse; Levitt, Jonathan B.; Jones, Liesl B.

2013-01-01

Research suggests that the medial dorsal nucleus (MD) of the thalamus influences pyramidal cell development in the prefrontal cortex (PFC) in an activity-dependent manner. The MD is reciprocally connected to the PFC. Many psychiatric disorders, such as schizophrenia, affect the PFC, and one of the most consistent findings in schizophrenia is a decrease in volume and neuronal number in the MD. Therefore, understanding the role the MD plays in the development of the PFC is important and may help in understanding the progression of psychiatric disorders that have their root in development. Focusing on the interplay between the MD and the PFC, this study examined the hypothesis that the MD plays a role in the dendritic development of pyramidal cells in the PFC. Unilateral electrolytic lesions of the MD in Long-Evans rat pups were made on postnatal day 4 (P4), and the animals developed to P60. We then examined dendritic morphology by examining MAP2 immunostaining and by using Golgi techniques to determine basilar dendrite number and spine density. Additionally, we examined pyramidal cell density in cingulate area 1 (Cg1), prelimbic region, and dorsolateral anterior cortex, which receive afferents from the MD. Thalamic lesions caused a mean MD volume decrease of 12.4% which led to a significant decrease in MAP2 staining in both superficial and deep layers in all 3 cortical areas. The lesions also caused a significant decrease in spine density and in the number of primary and secondary basilar dendrites on superficial and deep layer pyramidal neurons in all 3 regions. No significant difference was observed in pyramidal cell density in any of the regions or layers, but a nonsignificant increase in cell density was observed in 2 regions. Our data are thus consistent with the hypothesis that the MD plays a role in the development of the PFC and, therefore, may be a good model to begin to examine neurodevelopmental disorders such as autism and schizophrenia. PMID:23406908

Social, societal, and economic burden of mal de debarquement syndrome.

PubMed

Macke, Allison; LePorte, Andrew; Clark, Brian C

2012-07-01

Mal de debarquement syndrome (MdDS) is a disorder of phantom perception of self-motion of unknown cause. The purpose of this work was to describe the quality of life (QOL) of patients with MdDS and to estimate the economic costs associated with this disorder. A modified version of a QOL survey used for another neurological disease (multiple sclerosis; MSQOL-54) was used to assess the impact of MdDS on QOL in 101 patients. The estimated economic costs were based on self-reported direct and indirect costs of individuals living in the United States using Medicare reimbursement payment rates for 2011 in 79 patients. Patients with MdDS reported a poor overall QOL as indicated by a mean composite QOL score of 59.26 ± 1.89 (out of 100). The subcategories having the lowest QOL rating were role limitations due to physical problems (18.32 ± 3.20), energy (34.24 ± 1.47), and emotional problems (36.30 ± 4.00). The overall physical health composite score including balance was 49.40 ± 1.69, and the overall mental health composite score was 52.40 ± 1.83. The cost to obtain a diagnosis was $2,997 ± 337, which included requiring an average of 19 physician visits per patient. The direct cost of MdDS medical care was $826 ± 140 per patient per year, which mainly included diagnostic imaging and physician visits. The indirect costs (i.e., lost wages) were $9,781 ± 2,347 per patient per year. Among 65 patients who were gainfully employed when they acquired MdDS, the indirect costs were $11,888 ± 2,786 per patient per year. Thus, the total annual cost of the disorder ranged from $11,493 ± 2,341 to $13,561 ± 2,778 per patient per year depending on employment status prior to developing MdDS. MdDS negatively and dramatically impacts QOL, and also imposes a substantial economic burden on MdDS patients. These findings underscore the need for further basic and clinical research on MdDS.

Comparison of major depressive disorder and subthreshold depression among older adults in community long-term care.

PubMed

Lee, Mi Jin; Hasche, Leslie K; Choi, Sunha; Proctor, Enola K; Morrow-Howell, Nancy

2013-01-01

This study extends existing knowledge regarding the continuum between major depression (MD) and subthreshold depression (SD) by examining differences in symptomology and associative factors for a subpopulation of older adults with functional disability. Our sample consisted of clients age 60 and above entering public community long term care derived from the baseline survey of a longitudinal study (315 non-depressed, 74 MD, and 221 SD). We used the Diagnostic Interview Schedule to establish diagnoses of MD, the Center for Epidemiological Studies Depression Scale (CES-D) to assess SD, and other self-report measures to explore potential associative factors of demographics, comorbidity, social support, and stressors. No differences in CES-D identified symptoms occurred between the two groups. MD and SD were both associated with lower education, poorer social support, more severe medical conditions, and higher stress when compared to non-depressed older adults. Younger age and being female were associated solely with MD; whereas, worse perceived health and more trouble affording food were associated solely with SD. The only associative factor significantly different between MD and SD was age. Those with MD were more likely to be younger than those with SD. Our findings of symptom profiles and associative factors lend support to the continuum notion of depression. Identification of only older adults within the community long-term care service system who meet criteria for MD would leave many older adults, who also face multiple comorbidities, high levels of stress and social isolation, and substantial depressive symptoms undiagnosed and untreated.

Genome-wide identification and analysis of the SBP-box family genes in apple (Malus × domestica Borkh.).

PubMed

Li, Jun; Hou, Hongmin; Li, Xiaoqin; Xiang, Jiang; Yin, Xiangjing; Gao, Hua; Zheng, Yi; Bassett, Carole L; Wang, Xiping

2013-09-01

SQUAMOSA promoter binding protein (SBP)-box genes encode a family of plant-specific transcription factors and play many crucial roles in plant development. In this study, 27 SBP-box gene family members were identified in the apple (Malus × domestica Borkh.) genome, 15 of which were suggested to be putative targets of MdmiR156. Plant SBPs were classified into eight groups according to the phylogenetic analysis of SBP-domain proteins. Gene structure, gene chromosomal location and synteny analyses of MdSBP genes within the apple genome demonstrated that tandem and segmental duplications, as well as whole genome duplications, have likely contributed to the expansion and evolution of the SBP-box gene family in apple. Additionally, synteny analysis between apple and Arabidopsis indicated that several paired homologs of MdSBP and AtSPL genes were located in syntenic genomic regions. Tissue-specific expression analysis of MdSBP genes in apple demonstrated their diversified spatiotemporal expression patterns. Most MdmiR156-targeted MdSBP genes, which had relatively high transcript levels in stems, leaves, apical buds and some floral organs, exhibited a more differential expression pattern than most MdmiR156-nontargeted MdSBP genes. Finally, expression analysis of MdSBP genes in leaves upon various plant hormone treatments showed that many MdSBP genes were responsive to different plant hormones, indicating that MdSBP genes may be involved in responses to hormone signaling during stress or in apple development. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

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

Pang, Yuan-Ping, E-mail: pang@mayo.edu

Highlights: • Reducing atomic masses by 10-fold vastly improves sampling in MD simulations. • CLN025 folded in 4 of 10 × 0.5-μs MD simulations when masses were reduced by 10-fold. • CLN025 folded as early as 96.2 ns in 1 of the 4 simulations that captured folding. • CLN025 did not fold in 10 × 0.5-μs MD simulations when standard masses were used. • Low-mass MD simulation is a simple and generic sampling enhancement technique. - Abstract: CLN025 is one of the smallest fast-folding proteins. Until now it has not been reported that CLN025 can autonomously fold to its nativemore » conformation in a classical, all-atom, and isothermal–isobaric molecular dynamics (MD) simulation. This article reports the autonomous and repeated folding of CLN025 from a fully extended backbone conformation to its native conformation in explicit solvent in multiple 500-ns MD simulations at 277 K and 1 atm with the first folding event occurring as early as 66.1 ns. These simulations were accomplished by using AMBER forcefield derivatives with atomic masses reduced by 10-fold on Apple Mac Pros. By contrast, no folding event was observed when the simulations were repeated using the original AMBER forcefields of FF12SB and FF14SB. The results demonstrate that low-mass MD simulation is a simple and generic technique to enhance configurational sampling. This technique may propel autonomous folding of a wide range of miniature proteins in classical, all-atom, and isothermal–isobaric MD simulations performed on commodity computers—an important step forward in quantitative biology.« less

Magnetic phase diagrams of amorphous (Ni100-xFex)-metalloid alloys: The key role of the electronic density of states at the Fermi level for the onset of magnetic order

NASA Astrophysics Data System (ADS)

Kiss, L. F.; Bakonyi, I.

2017-11-01

There have been extended studies on the appearance of ferromagnetism in transition-metal-metalloid (MD) glasses. In particular, the paramagnetic (PM) to ferromagnetic (FM) transition has been investigated on numerous (Ni100-xFex)-MD alloys upon the introduction of Fe where MD can represent a combination of various metalloid elements, while keeping the metal/metalloid ratio constant. It has been reported that adding a sufficient amount of Fe to a Pauli PM Ni-MD alloy matrix first induces a spin-glass (SG) state at low temperatures which goes over to a PM state at higher temperatures. Beyond a certain Fe content, xc, the SG state transforms to a FM state upon increasing the temperature. By plotting the characteristic transition temperatures as a function of the Fe content, a magnetic phase diagram can be constructed for each Ni-Fe-MD system which has a multicritical point (MCP) at xc. By using the reported magnetic phase diagrams of various Ni-Fe-MD alloy systems, it is shown that the critical Fe content, xc scales inversely with the density of states at the Fermi level, N(EF), of the parent Ni-MD matrix. This means that the higher the N(EF), the lower the critical Fe content to induce ferromagnetism in the Ni-MD matrix. This is then discussed in terms of the Stoner enhancement factor, S, which characterizes the tendency of the matrix to become ferromagnetic.

Vestibular Evoked Myogenic Potentials (VEMP) Can Detect Asymptomatic Saccular Hydrops

PubMed Central

Lin, Ming-Yee; Timmer, Ferdinand C. A.; Oriel, Brad S.; Zhou, Guangwei; Guinan, John J.; Kujawa, Sharon G.; Herrmann, Barbara S.; Merchant, Saumil N.; Rauch, Steven D.

2009-01-01

Objective The objective of this study was to explore the useful of vestibular evoked myogenic potential (VEMP) testing for detecting endolymphatic hydrops, especially in the second ear of patients with unilateral Ménière disease (MD). Methods This study was performed at a tertiary care academic medical center. Part I consisted of postmortem temporal bone specimens from the temporal bone collection of the Massachusetts Eye & Ear Infirmary; part II consisted of consecutive consenting adult patients (n = 82) with unilateral MD by American Academy of Otolaryngology–Head and Neck Surgery criteria case histories. Out-come measures consisted of VEMP thresholds in patients and histologic saccular endolymphatic hydrops in postmortem temporal bones. Results Saccular hydrops was observed in the asymptomatic ear in six of 17 (35%) of temporal bones from donors with unilateral MD. Clinic patients with unilateral MD showed elevated mean VEMP thresholds and altered VEMP tuning in their symptomatic ears and, to a lesser degree, in their asymptomatic ears. Specific VEMP frequency and tuning criteria were used to define a “Ménière-like” response. This “Ménière-like” response was seen in 27% of asymptomatic ears of our patients with unilateral MD. Conclusions Bilateral involvement is seen in approximately one third of MD cases. Saccular hydrops appears to precede symptoms in bilateral MD. Changes in VEMP threshold and tuning appear to be sensitive to these structural changes in the saccule. If so, then VEMP may be useful as a detector of asymptomatic saccular hydrops and as a predictor of evolving bilateral MD. PMID:16735912

Sex-dependent effects of neonatal maternal deprivation on endocannabinoid levels in the adipose tissue: influence of diet.

PubMed

Mela, Virginia; Piscitelli, Fabiana; Berzal, Alvaro Llorente; Chowen, Julie; Silvestri, Cristoforo; Viveros, Maria Paz; Di Marzo, Vincenzo

2016-08-01

Maternal deprivation (MD) during neonatal life has diverse long-term effects, including modification of metabolism. We have previously reported that MD modifies the metabolic response to high-fat diet (HFD) intake, with this response being different between males and females, while previous studies indicate that in mice with HFD-induced obesity, endocannabinoid (EC) levels are markedly altered in various brown and white adipose tissue depots. Here, we analyzed the effects of MD (24 h at postnatal day 9), alone or in combination with a HFD from weaning until the end of the experiment in Wistar rats of both sexes. Brown and white perirenal and subcutaneous adipose tissues were collected and the levels of anandamide (AEA), 2-arachidonoylglycerol (2-AG), palmitoylethanolamide (PEA), and oleoylethanolamide (OEA) were determined. In males, MD increased the content of OEA in brown and 2-AG in subcutaneous adipose tissues, while in females the content of 2-AG was increased in perirenal fat. Moreover, in females, MD decreased AEA and OEA levels in perirenal and subcutaneous adipose tissues, respectively. HFD decreased the content of 2-AG in brown fat of both sexes and OEA in brown and subcutaneous adipose tissue of control females. In contrast, in subcutaneous fat, HFD increased AEA levels in MD males and OEA levels in control and MD males. The present results show for the first time that MD and HFD induce sex-dependent effects on the main ECs, AEA, and 2-AG, and of AEA-related mediators, OEA and PEA, in the rat brown and white (visceral and subcutaneous) adipose tissues.

Ligand Binding Pathways and Conformational Transitions of the HIV Protease.

PubMed

Miao, Yinglong; Huang, Yu-Ming M; Walker, Ross C; McCammon, J Andrew; Chang, Chia-En A

2018-03-06

It is important to determine the binding pathways and mechanisms of ligand molecules to target proteins to effectively design therapeutic drugs. Molecular dynamics (MD) is a promising computational tool that allows us to simulate protein-drug binding at an atomistic level. However, the gap between the time scales of current simulations and those of many drug binding processes has limited the usage of conventional MD, which has been reflected in studies of the HIV protease. Here, we have applied a robust enhanced simulation method, Gaussian accelerated molecular dynamics (GaMD), to sample binding pathways of the XK263 ligand and associated protein conformational changes in the HIV protease. During two of 10 independent GaMD simulations performed over 500-2500 ns, the ligand was observed to successfully bind to the protein active site. Although GaMD-derived free energy profiles were not fully converged because of insufficient sampling of the complex system, the simulations still allowed us to identify relatively low-energy intermediate conformational states during binding of the ligand to the HIV protease. Relative to the X-ray crystal structure, the XK263 ligand reached a minimum root-mean-square deviation (RMSD) of 2.26 Å during 2.5 μs of GaMD simulation. In comparison, the ligand RMSD reached a minimum of only ∼5.73 Å during an earlier 14 μs conventional MD simulation. This work highlights the enhanced sampling power of the GaMD approach and demonstrates its wide applicability to studies of drug-receptor interactions for the HIV protease and by extension many other target proteins.

Fast recovery of free energy landscapes via diffusion-map-directed molecular dynamics.

PubMed

Preto, Jordane; Clementi, Cecilia

2014-09-28

The reaction pathways characterizing macromolecular systems of biological interest are associated with high free energy barriers. Resorting to the standard all-atom molecular dynamics (MD) to explore such critical regions may be inappropriate as the time needed to observe the relevant transitions can be remarkably long. In this paper, we present a new method called Extended Diffusion-Map-directed Molecular Dynamics (extended DM-d-MD) used to enhance the sampling of MD trajectories in such a way as to rapidly cover all important regions of the free energy landscape including deep metastable states and critical transition paths. Moreover, extended DM-d-MD was combined with a reweighting scheme enabling to save on-the-fly information about the Boltzmann distribution. Our algorithm was successfully applied to two systems, alanine dipeptide and alanine-12. Due to the enhanced sampling, the Boltzmann distribution is recovered much faster than in plain MD simulations. For alanine dipeptide, we report a speedup of one order of magnitude with respect to plain MD simulations. For alanine-12, our algorithm allows us to highlight all important unfolded basins in several days of computation when one single misfolded event is barely observable within the same amount of computational time by plain MD simulations. Our method is reaction coordinate free, shows little dependence on the a priori knowledge of the system, and can be implemented in such a way that the biased steps are not computationally expensive with respect to MD simulations thus making our approach well adapted for larger complex systems from which little information is known.

Multifunctional oxidosqualene cyclases and cytochrome P450 involved in the biosynthesis of apple fruit triterpenic acids.

PubMed

Andre, Christelle M; Legay, Sylvain; Deleruelle, Amélie; Nieuwenhuizen, Niels; Punter, Matthew; Brendolise, Cyril; Cooney, Janine M; Lateur, Marc; Hausman, Jean-François; Larondelle, Yvan; Laing, William A

2016-09-01

Apple (Malus × domestica) accumulates bioactive ursane-, oleanane-, and lupane-type triterpenes in its fruit cuticle, but their biosynthetic pathway is still poorly understood. We used a homology-based approach to identify and functionally characterize two new oxidosqualene cyclases (MdOSC4 and MdOSC5) and one cytochrome P450 (CYP716A175). The gene expression patterns of these enzymes and of previously described oxidosqualene cyclases were further studied in 20 apple cultivars with contrasting triterpene profiles. MdOSC4 encodes a multifunctional oxidosqualene cyclase producing an oleanane-type triterpene, putatively identified as germanicol, as well as β-amyrin and lupeol, in the proportion 82 : 14 : 4. MdOSC5 cyclizes 2,3-oxidosqualene into lupeol and β-amyrin at a ratio of 95 : 5. CYP716A175 catalyses the C-28 oxidation of α-amyrin, β-amyrin, lupeol and germanicol, producing ursolic acid, oleanolic acid, betulinic acid, and putatively morolic acid. The gene expression of MdOSC1 was linked to the concentrations of ursolic and oleanolic acid, whereas the expression of MdOSC5 was correlated with the concentrations of betulinic acid and its caffeate derivatives. Two new multifuntional triterpene synthases as well as a multifunctional triterpene C-28 oxidase were identified in Malus × domestica. This study also suggests that MdOSC1 and MdOSC5 are key genes in apple fruit triterpene biosynthesis. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Lipid droplet-associated gene expression and chromatin remodelling in LIPASE 5'-upstream region from beginning- to mid-endodormant bud in 'Fuji' apple.

PubMed

Saito, Takanori; Wang, Shanshan; Ohkawa, Katsuya; Ohara, Hitoshi; Ikeura, Hiromi; Ogawa, Yukiharu; Kondo, Satoru

2017-11-01

We found that lipid accumulation in the meristem region and the expression of MdLIP2A, which appears to be regulated by chromatin remodeling, coincided with endodormancy induction in the 'Fuji' apple. In deciduous trees, including apples (Malus × domestica Borkh.), lipid accumulation in the meristem region towards endodormancy induction has been thought to be an important process for the acquisition of cold tolerance. In this study, we conducted histological staining of crude lipids in the meristem region of 'Fuji' apples and found that lipid accumulation coincided with endodormancy induction. Since a major component of lipid bodies (triacylglycerol) is esterified fatty acids, we analysed fatty acid-derived volatile compounds and genes encoding fatty acid-modifying enzymes (MdLOX1A and MdHPL2A); the reduction of lipid breakdown also coincided with endodormancy induction. We then characterised the expression patterns of lipid body-regulatory genes MdOLE1 and MdLIP2A during endodormancy induction and found that the expression of MdLIP2A correlated well with lipid accumulation towards endodormancy induction. Based on these results, we conducted chromatin remodelling studies and localized the cis-element in the 5'-upstream region of MdLIP2A to clarify its regulatory mechanism. Finally, we revealed that chromatin was concentrated - 764 to - 862 bp of the 5'-upstream region of MdLIP2A, which harbours the GARE [gibberellin responsive MYB transcription factor binding site] and CArG [MADS-box transcription factor binding site] motifs-meristem development-related protein-binding sites.

Characterization of an apple TT2-type R2R3 MYB transcription factor functionally similar to the poplar proanthocyanidin regulator PtMYB134.

PubMed

Gesell, Andreas; Yoshida, Kazuko; Tran, Lan T; Constabel, C Peter

2014-09-01

The apple MdMYB9 gene encodes a positive regulator of proanthocyanidin synthesis that activates anthocyanidin reductase promoters from apple and poplar via interaction with basic helix-loop-helix proteins. The regulation of proanthocyanidins (PAs, condensed tannins) is of great importance in food plants due to the many benefits of PAs in the human diet. Two candidate flavonoid MYB regulators, MdMYB9 and MdMYB11, were cloned from apple (Malus × domestica) based on their similarity to known MYB PA regulators. Transcript accumulation of both MdMYB9 and MdMYB11 was induced by high light and wounding, similar to the poplar (Populus spp) PA regulator PtMYB134. In transient activation assays with various basic helix-loop-helix (bHLH) co-regulators, MdMYB9 activated apple and poplar anthocyanidin reductase (ANR) promoters, while MdMYB11 showed no activity. Potential transcription factor binding elements were found within several ANR promoters, and the importance of the bHLH binding site (E-box) on ANR promoter activation was demonstrated via mutational analysis. The ability of MdMYB9 and PtMYB134 to reciprocally activate ANR promoters from both apple and poplar and to partner with heterologous bHLH co-factors from these plants confirms the high degree of conservation of PA regulatory complexes across species. The similarity in apple and poplar PA regulation suggests that regulatory genes from poplar could be effectively employed for metabolic engineering of the PA pathway in apple.

Decline of the Mediterranean diet at a time of economic crisis. Results from the Moli-sani study.

PubMed

Bonaccio, M; Di Castelnuovo, A; Bonanni, A; Costanzo, S; De Lucia, F; Persichillo, M; Zito, F; Donati, M B; de Gaetano, G; Iacoviello, L

2014-08-01

Adherence to Mediterranean diet (MD) is reportedly declining in the last decades. We aimed to investigate the adherence to MD over the period 2005-2010 and exploring the possible role of the global economic crisis in accounting for the changing in the dietary habits in Italy. Cross-sectional analysis in a population-based cohort study which randomly recruited 21,001 southern Italian citizens enrolled within the Moli-sani study. Food intake was determined by the Italian EPIC food frequency questionnaire. Adherence to MD was appraised by the Italian Mediterranean Index (IMI). A wealth score was derived to evaluate the economic position and used together with other socioeconomic indicators. Highest prevalence of adherence to MD was observed during the years 2005-2006 (31.3%) while the prevalence dramatically fell down in the years 2007-2010 (18.3%; P<0.0001). The decrease was stronger in the elderly, less affluent groups, and among those living in urban areas. Accordingly, we observed that in 2007-2010 socioeconomic indicators were strongly associated with higher adherence to MD, whereas no association was detected in the years before the economic crisis began; both wealth score and education were major determinants of high adherence to MD with 31% (95%CI: 18-46%) higher adherence to this pattern within the wealthier group compared to the less affluent category. Adherence to MD has considerably decreased over the last few years. In 2007-2010 socioeconomic indicators have become major determinants of adherence to MD, a fact likely linked to the economic downturn. Copyright © 2014 Elsevier B.V. All rights reserved.

Back Schools for chronic non-specific low back pain.

PubMed

Parreira, Patrícia; Heymans, Martijn W; van Tulder, Maurits W; Esmail, Rosmin; Koes, Bart W; Poquet, Nolwenn; Lin, Chung-Wei Christine; Maher, Christopher G

2017-08-03

Many people with low back pain (LBP) become frequent users of healthcare services in their attempt to find treatments that minimise the severity of their symptoms. Back School consists of a therapeutic programme given to groups of people that includes both education and exercise. However, the content of Back School has changed over time and appears to vary widely today. This review is an update of a Cochrane review of randomised controlled trials (RCTs) evaluating the effectiveness of Back School. We split the Cochrane review into two reviews, one focusing on acute and subacute LBP, and one on chronic LBP. The objective of this systematic review was to determine the effect of Back School on pain and disability for adults with chronic non-specific LBP; we included adverse events as a secondary outcome. In trials that solely recruited workers, we also examined the effect on work status. We searched for trials in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, two other databases and two trials registers to 15 November 2016. We also searched the reference lists of eligible papers and consulted experts in the field of LBP management to identify any potentially relevant studies we may have missed. We placed no limitations on language or date of publication. We included only RCTs and quasi-RCTs evaluating pain, disability, and/or work status as outcomes. The primary outcomes for this update were pain and disability, and the secondary outcomes were work status and adverse events. Two review authors independently performed the 'Risk of bias' assessment of the included studies using the 'Risk of bias' assessment tool recommended by The Cochrane Collaboration. We summarised the results for the short-, intermediate-, and long-term follow-ups. We evaluated the overall quality of evidence using the GRADE approach. For the outcome pain, at short-term follow-up, we found very low-quality evidence that Back School is more effective than no treatment (mean difference (MD) -6.10, 95% confidence interval (CI) -10.18 to -2.01). However, we found very low-quality evidence that there is no significant difference between Back School and no treatment at intermediate-term (MD -4.34, 95% CI -14.37 to 5.68) or long-term follow-up (MD -12.16, 95% CI -29.14 to 4.83). There was very low-quality evidence that Back School reduces pain at short-term follow-up compared to medical care (MD -10.16, 95% CI -19.11 to -1.22). Very low-quality evidence showed there to be no significant difference between Back School and medical care at intermediate-term (MD -9.65, 95% CI -22.46 to 3.15) or long-term follow-up (MD -5.71, 95% CI -20.27 to 8.84). We found very low-quality evidence that Back School is no more effective than passive physiotherapy at short-term (MD 1.96, 95% CI -9.51 to 13.43), intermediate-term (MD -16.89, 95% CI -66.56 to 32.79), or long-term follow-up (MD -12.86, 95% CI -61.22 to 35.50). There was very low-quality evidence that Back School is no better than exercise at short- term follow-up (MD -2.06, 95% CI -14.58 to 10.45). There was low-quality evidence that Back School is no better than exercise at intermediate-term (MD -4.46, 95% CI -19.44 to 10.52) and long-term follow-up (MD 4.58, 95% CI -0.20 to 9.36).For the outcome disability, we found very low-quality evidence that Back School is no more effective than no treatment at intermediate-term (MD -5.92, 95% CI -12.08 to 0.23) and long-term follow-up (MD -7.36, 95% CI -22.05 to 7.34); medical care at short-term (MD -1.19, 95% CI -7.02 to 4.64) and long-term follow-up (MD -0.40, 95% CI -7.33 to 6.53); passive physiotherapy at short-term (MD 2.57, 95% CI -15.88 to 21.01) and intermediate-term follow-up (MD 6.88, 95% CI -4.86 to 18.63); and exercise at short-term (MD -1.65, 95% CI -8.66 to 5.37), intermediate-term (MD 1.57, 95% CI -3.86 to 7.00), and long-term follow-up (MD 4.54, 95% CI -4.44 to 13.52). We found very low-quality evidence of a small difference between Back School and no treatment at short-term follow-up (MD -3.38, 95% CI -6.70 to -0.05) and medical care at intermediate-term follow-up (MD -6.34, 95% CI -10.89 to -1.79). Still, at long-term follow-up there was very low-quality evidence that passive physiotherapy is better than Back School (MD 9.60, 95% CI 3.65 to 15.54).Few studies measured adverse effects. The results were reported as means without standard deviations or group size was not reported. Due to this lack of information, we were unable to statistically pool the adverse events data. Work status was not reported. Due to the low- to very low-quality of the evidence for all treatment comparisons, outcomes, and follow-up periods investigated, it is uncertain if Back School is effective for chronic low back pain. Although the quality of the evidence was mostly very low, the results showed no difference or a trivial effect in favour of Back School. There are myriad potential variants on the Back School approach regarding the employment of different exercises and educational methods. While current evidence does not warrant their use, future variants on Back School may have different effects and will need to be studied in future RCTs and reviews.

52 Loop-mediated isothermal amplification PCR (LAMP) for the rapid identification of invasive meningococcal disease in the emergency department.

PubMed

Waterfield, Thomas; Patenall, Bethany; McKenna, James; Fairley, Derek

2017-12-01

Despite successful vaccination programmes meningococcal disease (MD) remains the leading infectious cause of septicaemia and death in children in the UK and Ireland. 1,2 The early diagnosis of MD significantly improves outcomes with reduced morbidity and mortality. 1,2 The early stages of MD are often indistinguishable from a simple viral illness making an early positive diagnosis of MD difficult. 1 Hibergene have developed a commercially available bedside Loop-mediated isothermal AMPlification PCR (LAMP-MD) test that is a highly sensitive 0.89 (95%CI 0.72-0.96) and specific 1.0 (95%CI 0.97-1.0) for identifying children with invasive MD (4) (figure 1).emermed;34/12/A895-a/F1F1F1Figure 1 AIMS: The aims of this RCEM funded study were:Assess the ease of use and suitability for the EDDetermine the time taken to perform the testIndependently verify LAMP-MD performance against TaqMan quantitative PCR. The LAMP-MD was assessed for practicality and ease of use within the ED including an assessment of training needs, footprint and health and safety requirements.For verification of the Hibergene LAMP-MD analyser and assay we used dry nasopharyngeal swabs sent for viral screening. Additional verification was undertaken using N. meningitidis genomic DNA spiked over a range of concentrations. This included serotypes A, B, C, W, X and Y and a dilution series to determine the limit of detection. All samples were then analysed using real time TaqMan qPCR. The LAMP-MD analyser was easy to use and could be accommodated in the EDThe mean time for detection of Meningococcal DNA was 14.01 minDetection of meningococcal serogroups A, B, C, W, X and Z was confirmedThe detection limit for dry nasopharyngeal swabs was below 2 genomic copies per µlNo non-specific amplification was observed in 17 randomly selected negative clinical swabsThe LAMP-MD assay was 100% sensitive and specific relative to real-time TaqMAN PCR. LAMP-MD is a practical, rapid point of care test that can reliably detect all Meningococcal serotypes in less than 15 min.Funding has been secured to perform a PERUKI supported study to investigate the potential for LAMP-MD in the diagnosis of meningococcal disease in children. Meningitis Research Foundation. Meningococcal Meningitis and Septicaemia Guidance Notes 2014.Ó Maoldomhnaigh, et al. Invasive meningococcal disease in children in Ireland . PMID: 27566800.NICE. Management of petechial rash .Bourke TW, et al. Diagnostic accuracy of loop-mediated isothermal amplification as a near-patient test for meningococcal disease in children . PMID: 25728843. © 2017, 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.

Practices of Management Development: A Malaysian Case Study

ERIC Educational Resources Information Center

Law, Kian Aun

2008-01-01

This paper deals with a case study of Management Development (MD) practices at Malaysian Assurance Alliance (MAA). The aim of this research is to investigate how a large Malaysian insurance corporation developed and integrated MD initiatives with current organizational needs and tasks. Attempts were made to map and categorize the MD initiatives…

Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer

DTIC Science & Technology

2017-01-01

research professor, 1 post-doctoral fellow, and 3 research associates. We have worked closely with our surgery, medical oncology , and pathology...MD – project PI (40% effort) Personnel 2. John Yim, MD – CoH Surgical Oncology (5% effort) 3. Joanne Mortimer, MD – CoH Medical Oncology (no

33 CFR 110.71 - Jacobs Nose Cove, Elk River, Md.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Jacobs Nose Cove, Elk River, Md. 110.71 Section 110.71 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71 Jacobs Nose Cove, Elk River, Md. The water...

33 CFR 110.71 - Jacobs Nose Cove, Elk River, Md.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Jacobs Nose Cove, Elk River, Md. 110.71 Section 110.71 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71 Jacobs Nose Cove, Elk River, Md. The water...

33 CFR 110.70a - Northeast River, North East, Md.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Northeast River, North East, Md. 110.70a Section 110.70a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.70a Northeast River, North East, Md. The water...

33 CFR 110.70a - Northeast River, North East, Md.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Northeast River, North East, Md. 110.70a Section 110.70a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.70a Northeast River, North East, Md. The water...

33 CFR 110.71 - Jacobs Nose Cove, Elk River, Md.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Jacobs Nose Cove, Elk River, Md. 110.71 Section 110.71 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71 Jacobs Nose Cove, Elk River, Md. The water...

33 CFR 110.70a - Northeast River, North East, Md.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Northeast River, North East, Md. 110.70a Section 110.70a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.70a Northeast River, North East, Md. The water...

33 CFR 110.71 - Jacobs Nose Cove, Elk River, Md.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Jacobs Nose Cove, Elk River, Md. 110.71 Section 110.71 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71 Jacobs Nose Cove, Elk River, Md. The water...

33 CFR 110.70a - Northeast River, North East, Md.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Northeast River, North East, Md. 110.70a Section 110.70a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.70a Northeast River, North East, Md. The water...

33 CFR 110.71 - Jacobs Nose Cove, Elk River, Md.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Jacobs Nose Cove, Elk River, Md. 110.71 Section 110.71 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71 Jacobs Nose Cove, Elk River, Md. The water...

Metadata (MD)

Treesearch

Robert E. Keane

2006-01-01

The Metadata (MD) table in the FIREMON database is used to record any information about the sampling strategy or data collected using the FIREMON sampling procedures. The MD method records metadata pertaining to a group of FIREMON plots, such as all plots in a specific FIREMON project. FIREMON plots are linked to metadata using a unique metadata identifier that is...

33 CFR 165.509 - Security Zone; Severn River and College Creek, Annapolis, MD.

Code of Federal Regulations, 2010 CFR

2010-07-01

... College Creek, Annapolis, MD. 165.509 Section 165.509 Navigation and Navigable Waters COAST GUARD... § 165.509 Security Zone; Severn River and College Creek, Annapolis, MD. (a) Definitions. For purposes of... the Naval Academy waterfront. This security zone includes the waters of College Creek eastward of the...

77 FR 24838 - Safety Zone; Magothy River, Sillery Bay, MD

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-26

...-AA00 Safety Zone; Magothy River, Sillery Bay, MD AGENCY: Coast Guard, DHS. ACTION: Final rule. SUMMARY: The Coast Guard is establishing a safety zone in certain waters of the Magothy River, in Sillery Bay... a notice of proposed rulemaking (NPRM) entitled ``Safety Zone; Magothy River, Sillery Bay, MD'' in...

Management of Suicide-Related Events during Deployment

DTIC Science & Technology

2014-02-01

progress on site tasks. In addition, Emily Biggs , a Master’s level Research Assistant is assisting with site-specific study activities. At the...Bowles, Ph.D., ABPP; John Bradley, M.D.; Russell B. Carr, M.D.; Charles C. Engel, M.D., MPH; David A. Jobes, Ph.D., ABPP; Chris Martin, LCDR; Kim Ruocco

75 FR 12766 - National Center on Minority Health and Health Disparities; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-17

..., Bethesda, MD 20892. (Virtual Meeting) Contact Person: Prabha L. Atreya, PhD, Chief, Office of Scientific... Health, 6706 Democracy Blvd. 800, Bethesda, MD 20892. (Virtual Meeting) Contact Person: Prabha L. Atreya... Democracy Boulevard, Suite 800, Bethesda, MD 20892. (Virtual Meeting) Contact Person: Prabha L. Atreya, PhD...

Characterizing a point mutation within the UL5 gene that reduces in vivo replication and MD incidence

USDA-ARS?s Scientific Manuscript database

Marek’s disease virus (MDV) is an oncogenic alphaherpesvirus of chickens and the causative agent for Marek’s disease (MD). Vaccination is the primary method to control MD. Despite the success of vaccination, more virulent field strains are evolving, requiring the development of new vaccines. Attenua...

77 FR 29692 - Segun M. Rasaki, M.D.; Decision and Order

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-18

... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 12-28] Segun M. Rasaki, M.D...'s action at which he may ultimately prevail.'' Kamal Tiwari, M.D., 76 FR 71604, 71606 (2011); see....100(b), I order that DEA Certificate of Registration BR9738595, issued to Segun M. Rasaki, M.D., be...

77 FR 1411 - Approval and Promulgation of Air Quality Implementation Plans; District of Columbia, Maryland...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-10

...; Determinations of Attainment of the 1997 Fine Particle Standard for the Metropolitan Washington, DC-MD-VA and...-Maryland-Virginia (DC-MD-VA) fine particle (PM 2.5 ) nonattainment area and the Martinsburg-Hagerstown... determined that the Metropolitan Washington, District of Columbia-Maryland-Virginia (DC-MD-VA) fine particle...

78 FR 17996 - MCM Rail Services LLC-Petition for Retroactive Exemption-In Sparrows Point, Md.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-25

... LLC--Petition for Retroactive Exemption--In Sparrows Point, Md. AGENCY: Surface Transportation Board... of rail line in Sparrows Point, Md. (the Line). DATES: MCM's supplemental information is due by April... Railroad, and currently named the Baltimore Industrial Railway, is located at 1430 Sparrows Point Boulevard...

77 FR 20025 - Draft Guidance for Industry on Compliance Policy for Reporting Drug Sample Distribution...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-03

... Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 2201, Silver Spring, MD... Evaluation and Research (CBER), Food and Drug Administration, 1401 Rockville Pike, Suite 200N, Rockville, MD... Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 4288, Silver Spring, MD...

Comparative transcriptomics of genetically divergent lines of chickens in response to Marek’s disease virus challenge at cytolytic phase

USDA-ARS?s Scientific Manuscript database

Marek’s disease (MD) remains an economically significant threat to poultry industry worldwide. Genetic resistance to MD is a promising alternative strategy to augment current control measures (vaccination and management). However, only a few functional genes reportedly conferring MD resistance have ...

33 CFR 110.70a - Northeast River, North East, Md.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Northeast River, North East, Md. 110.70a Section 110.70a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.70a Northeast River, North East, Md. The water...

77 FR 2987 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-20

..., National Institutes of Health, Room 761, 6707 Democracy Boulevard, Bethesda, MD 20892-5452, (301) 594-4719... Democracy Plaza, 6707 Democracy Boulevard, Bethesda, MD 20892, (Telephone Conference Call). Contact Person... Health, Room 756, 6707 Democracy Boulevard, Bethesda, MD 20892-5452, (301) 594-7682, [email protected

77 FR 31629 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-29

... Institutes of Health, Two Democracy Plaza, 6707 Democracy Boulevard, Bethesda, MD 20892 (Telephone Conference..., National Institutes of Health, Room 756, 6707 Democracy Boulevard, Bethesda, MD 20892-5452, (301) 594-7682... 760, 6707 Democracy Boulevard, Bethesda, MD 20892-5452, (301) 594-3993, [email protected] . Name of...

76 FR 71374 - Joseph Giacchino, M.D.; Decision and Order

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-17

... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 10-54] Joseph Giacchino, M.D.; Decision and Order On July 9, 2010, Administrative Law Judge (ALJ) Timothy D. Wing, issued the attached... prevail. See, e.g., Bourne Pharmacy, 72 FR 18,273, 18,274 (2007); Agostino Carlucci, M.D., 49 FR 33,184...

75 FR 30860 - Shepard Ginandes, M.D.; Revocation of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-02

... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 10-14] Shepard Ginandes, M.D... Administration, issued an Order to Show Cause and Immediate Suspension of Registration to Shepard Ginandes, M.D... right to a hearing.'' Id. (citing 21 CFR 1301.43(d) & (e)). On September 30, 2009, the Order was served...

Marek's disease virus immunosuppression alters host cellular responses and immune gene expression in the skin of infected chickens

USDA-ARS?s Scientific Manuscript database

Marek’s disease (MD) is a highly contagious lymphoproliferative and neuropathic disease of chickens. The feather follicle epithelium (FFE) is the only anatomical site within the host where infectious enveloped cell-free MD virus (MDV) particles are produced and disseminated into the environment. MD ...

76 FR 51412 - Joe C. Fermo, M.D.; Revocation of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-18

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Joe C. Fermo, M.D.; Revocation of... Enforcement Administration, issued an Order to Show Cause to Joe C. Fermo, M.D. (Registrant), of Tulsa... Order at 1 (citing 21 U.S.C. 823(f) and 824(a)(4)). The Show Cause Order specifically alleged that on...

77 FR 63290 - Foreign-Trade Zone 74-Baltimore, MD, Authorization of Production Activity, J.D. Neuhaus LP...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-16

... DEPARTMENT OF COMMERCE Foreign-Trade Zones Board [B-47-2012] Foreign-Trade Zone 74--Baltimore, MD, Authorization of Production Activity, J.D. Neuhaus LP, (Overhead Lifting Equipment Production), Sparks, MD On June 13, 2012, the Baltimore Development Corporation, grantee of FTZ 74, submitted a notification of...

77 FR 24972 - National Institute of Mental Health Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-26

..., Neuroscience Center, 6001 Executive Boulevard, Conference Room C/D/E, Rockville, MD 20852. Closed: 1:15 p.m. to..., Neuroscience Center, 6001 Executive Boulevard, Conference Room C/D/E, Rockville, MD 20852. Contact Person: Jane... Health, NIH, Neuroscience Center, 6001 Executive Blvd., Room 6154, MSC 9609, Bethesda, MD 20892-9609, 301...

76 FR 51379 - National Institute of Mental Health Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-18

..., Neuroscience Center, 6001 Executive Boulevard, Conference Room C/D/E, Rockville, MD 20852. Closed: 1:30 p.m. to..., Neuroscience Center, 6001 Executive Boulevard, Conference Room C/D/E, Rockville, MD 20852. Contact Person: Jane..., NIH, Neuroscience Center, 6001 Executive Blvd., Room 6154, MSC 9609, Bethesda, MD 20892-9609, 301-443...

78 FR 52551 - National Institute of Mental Health; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-23

...), Neuroscience Center, 6001 Executive Boulevard, Conference Room C/D/E, Rockville, MD 20852. Closed: 2:30 p.m. to..., Neuroscience Center, 6001 Executive Boulevard, Conference Room C/D/E, Rockville, MD 20852. Contact Person: Jane... Health, NIH, Neuroscience Center, 6001 Executive Blvd., Room 6154, MSC 9609, Bethesda, MD 20892-9609, 301...

77 FR 48998 - National Institute of Mental Health; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-15

... Neuroscience Center, 6001 Executive Boulevard, Conference Room C/D/E, Rockville, MD 20852. Closed: 2:30 p.m. to... Neuroscience Center, 6001 Executive Boulevard, Conference Room C/D/E, Rockville, MD 20852. Contact Person: Jane... Health, NIH, Neuroscience Center, 6001 Executive Blvd., Room 6154, MSC 9609, Bethesda, MD 20892-9609, 301...

No Girls Allowed: Women in Male-Dominated Majors Experience Increased Gender Harassment and Bias.

PubMed

Dresden, Brooke E; Dresden, Alexander Y; Ridge, Robert D; Yamawaki, Niwako

2018-06-01

The prevalence of gender harassment in male-dominated workforces has been well established, but little is known regarding the experiences of women in male-dominated majors within academia. The current study examines the experiences and gender-related biases of 146 male and female students in male-dominated (MD) and gender-equivalent (GE) majors. This study hypothesizes that men from MD majors, as opposed to GE majors, will exhibit more explicit and implicit bias regarding women in positions of power and authority, resulting in a higher prevalence of gender harassment towards women in MD majors. Results showed that there was no significant difference in self-reported explicit bias against women in positions of power and authority between men from MD and GE majors, but there was significantly more implicit bias among men from MD majors as opposed to GE majors. Additionally, women from MD majors experienced significantly more gender harassment than women from GE majors. Implications of these findings and suggestions to assist those working in education to combat these biases and instances of harassment are discussed.

Cognitive and Mathematical Profiles for Different Forms of Learning Difficulties

PubMed Central

Cirino, Paul T.; Fuchs, Lynn S.; Elias, John T.; Powell, Sarah R.; Schumacher, Robin F.

2014-01-01

The purpose of this study was to compare subgroups of students with various forms of learning difficulties (< 25th percentile) on cognitive and mathematics characteristics. Students with mathematics difficulty (MD, n = 105), reading difficulty (RD, n = 65), both (MDRD, n = 87), or neither (NoLD, n = 403) were evaluated on an array of cognitive measures (e.g., working memory and language) and on mathematics measures of foundational numerical competencies, computation, and problem solving. Results revealed expected level differences among groups in both domains: NoLD outperformed RD, and MD outperformed MDRD. Profile differences were noted among pairs of subgroups on cognitive measures. On mathematics measures, profile differences were noted between RD and other subgroups, but not between MD and MDRD subgroups. The most discriminating cognitive measures were processing speed and language; the most discriminating mathematics measures depended on the subgroups being compared. Results were further evaluated according to more severe (< 10th percentile) criteria for MD and RD, which generally affected level differences more than the profile patterns. Results have implications for understanding comorbid MD and RD and for conceptualizing core deficits in MD. PMID:23851137

[MD PhD programs: Providing basic science education for ophthalmologists].

PubMed

Spaniol, K; Geerling, G

2015-06-01

Enrollment in MD PhD programs offers the opportunity of a basic science education for medical students and doctors. These programs originated in the USA where structured programs have been offered for many years, but now German universities also run MD PhD programs. The MD PhD programs provided by German universities were investigated regarding entrance requirements, structure and financing modalities. An internet and telephone-based search was carried out. Out of 34 German universities 22 offered MD PhD programs. At 15 of the 22 universities a successfully completed course of studies in medicine was required for enrollment, 7 programs admitted medical students in training and 7 programs required a medical doctoral thesis, which had to be completed with at least a grade of magna cum laude in 3 cases. Financing required scholarships in many cases. Several German universities currently offer MD PhD programs; however, these differ considerably regarding entrance requirements, structure and financing. A detailed analysis investigating the success rates of these programs (e.g. successful completion and career paths of graduates) would be of benefit.

Constant-pH Molecular Dynamics Simulations for Large Biomolecular Systems

DOE PAGES

Radak, Brian K.; Chipot, Christophe; Suh, Donghyuk; ...

2017-11-07

We report that an increasingly important endeavor is to develop computational strategies that enable molecular dynamics (MD) simulations of biomolecular systems with spontaneous changes in protonation states under conditions of constant pH. The present work describes our efforts to implement the powerful constant-pH MD simulation method, based on a hybrid nonequilibrium MD/Monte Carlo (neMD/MC) technique within the highly scalable program NAMD. The constant-pH hybrid neMD/MC method has several appealing features; it samples the correct semigrand canonical ensemble rigorously, the computational cost increases linearly with the number of titratable sites, and it is applicable to explicit solvent simulations. The present implementationmore » of the constant-pH hybrid neMD/MC in NAMD is designed to handle a wide range of biomolecular systems with no constraints on the choice of force field. Furthermore, the sampling efficiency can be adaptively improved on-the-fly by adjusting algorithmic parameters during the simulation. Finally, illustrative examples emphasizing medium- and large-scale applications on next-generation supercomputing architectures are provided.« less

Hybrid particle-field molecular dynamics simulation for polyelectrolyte systems.

PubMed

Zhu, You-Liang; Lu, Zhong-Yuan; Milano, Giuseppe; Shi, An-Chang; Sun, Zhao-Yan

2016-04-14

To achieve simulations on large spatial and temporal scales with high molecular chemical specificity, a hybrid particle-field method was proposed recently. This method is developed by combining molecular dynamics and self-consistent field theory (MD-SCF). The MD-SCF method has been validated by successfully predicting the experimentally observable properties of several systems. Here we propose an efficient scheme for the inclusion of electrostatic interactions in the MD-SCF framework. In this scheme, charged molecules are interacting with the external fields that are self-consistently determined from the charge densities. This method is validated by comparing the structural properties of polyelectrolytes in solution obtained from the MD-SCF and particle-based simulations. Moreover, taking PMMA-b-PEO and LiCF3SO3 as examples, the enhancement of immiscibility between the ion-dissolving block and the inert block by doping lithium salts into the copolymer is examined by using the MD-SCF method. By employing GPU-acceleration, the high performance of the MD-SCF method with explicit treatment of electrostatics facilitates the simulation study of many problems involving polyelectrolytes.

Enhanced sampling simulations to construct free-energy landscape of protein-partner substrate interaction.

PubMed

Ikebe, Jinzen; Umezawa, Koji; Higo, Junichi

2016-03-01

Molecular dynamics (MD) simulations using all-atom and explicit solvent models provide valuable information on the detailed behavior of protein-partner substrate binding at the atomic level. As the power of computational resources increase, MD simulations are being used more widely and easily. However, it is still difficult to investigate the thermodynamic properties of protein-partner substrate binding and protein folding with conventional MD simulations. Enhanced sampling methods have been developed to sample conformations that reflect equilibrium conditions in a more efficient manner than conventional MD simulations, thereby allowing the construction of accurate free-energy landscapes. In this review, we discuss these enhanced sampling methods using a series of case-by-case examples. In particular, we review enhanced sampling methods conforming to trivial trajectory parallelization, virtual-system coupled multicanonical MD, and adaptive lambda square dynamics. These methods have been recently developed based on the existing method of multicanonical MD simulation. Their applications are reviewed with an emphasis on describing their practical implementation. In our concluding remarks we explore extensions of the enhanced sampling methods that may allow for even more efficient sampling.