Clinical Application of the PES/WES Index on Natural Teeth: Case Report and Literature Review

Directory of Open Access Journals (Sweden)

Alessandro Lanza

2017-01-01

Full Text Available The use of reliable indices to evaluate the aesthetic outcomes in the aesthetic area is an important and objective clinical aid to monitor the results over time. According to the literature various indices were proposed to evaluate aesthetic outcomes of implant-prosthetic rehabilitation of the anterior area like Peri-Implant and Crown Index [PICI], Implant Crown Aesthetic Index [ICAI], Pink Esthetic Score/White Esthetic Score [PES/WES], and Pink Esthetic Score [PES] but none of them was related to prosthetic rehabilitation on natural teeth. The aim of this study is to verify the validity of PES/WES index for natural tooth-prosthetic rehabilitation of the anterior area. As secondary objective, we proposed to evaluate the long-term predictability of this clinical application, one of which is presented below, following the analysis of the most currently accepted literature.

Oration ”Quotiens nova” of Pope Pius II (9 February 1459, Perugia). Edited and translated by Michael von Cotta-Schønberg. Preliminary edition, 5th version. (Orations of Enea Silvio Piccolomini / Pope Pius II; 30)

OpenAIRE

Cotta-Schønberg, Michael

2015-01-01

During his stay in Siena, in the spring of 1459, Pope Pius II received a number of embassies from the rulers of Europe coming to present the declaration of their lord’s obedience to the Apostolic See and the new pope. In his oration, Quotiens nova, to the ambassadors of Duke Louis of Savoy, the pope asserts the papal supremacy in all matters, spiritual and temporal, by virtue of the unlimited mission entrusted to the Apostle Peter by Jesus Christ. This mission and the power of the apostolic o...

A vueltas con la alfabetización visual: lenguaje y significado en las películas de Wes Anderson

Directory of Open Access Journals (Sweden)

José Gabriel Ferreras Rodríguez

2008-01-01

Full Text Available El presente artículo tiene por objetivo discutir algunos elementos del concepto de la alfabetización visual, aplicando, luego, las herramientas de análisis de imágenes a las películas de Wes Anderson, como ejemplos del manejo intencional de las imágenes para transmitir determinados significados. The present article aims to discuss, firstly, some elements encompassed in the definition of visual literary and, secondly, to apply some image analysis tools to Wes Anderson’s movies, as examples of intentional pictorial organization so as to convey specific meanings.

Through the Microscope: Understanding "The Tempest" in the Context of the Introduction to Pico della Mirandola’s "Oration on the Dignity of Man"

Directory of Open Access Journals (Sweden)

Michaela Krämer

2016-12-01

Full Text Available In the format of interpretation the creative laboratory of Shakespeare’s “The Tempest” is being revealed. By all accounts “The Tempest” has no specific sources. This study, however, supposes, that Shakespeare could refer to the basic concept and, from this perspective, even very closely rely on the details. Hence, it is proved, that the philosophical impulse of Shakespeare’s tragedy can be considered the introduction to the “Oration on the Dignity of Man” by Giovanni Pico della Mirandola, created for the forbidden later theological discussions on relevant topics in Rome (1486, which dealt with the possibility of moral self-determination and individual responsibility. Imposing the lines of the treatise by Pico on the images and plot of the drama by Shakespeare, we immediately notice a twisted three-dimensional image, the transition from abstract relationship to the visible processes of existence and consciousness, at the same time fantastic and real. This analysis is based on the statement, that “The Tempest” can be interpreted as the staging of memorable images of Pico. This statement is relevant to point of view, according to which Shakespeare could choose the idea of the Oration, or directly from the passage of the text. Shakespeare consciously goes beyond the ideas of Pico. If the quotations from the text of Pico are considered as a subtext, it immediately becomes evident that scene, characters and action of the play are based in some way on a complex conceptual scheme. With the underlying meaning of the Oration by Pico, “The Tempest” is a powerful creative experiment and a reasonable appeal to the uniqueness of human life and spiritual freedom of a man. Thus, this study, without resorting to discuss specific aspects of the play, aspires to promote scientific debate about its hidden meaning.

Novel Genetic Variants of Sporadic Atrial Septal Defect (ASD) in a Chinese Population Identified by Whole-Exome Sequencing (WES).

Science.gov (United States)

Liu, Yong; Cao, Yu; Li, Yaxiong; Lei, Dongyun; Li, Lin; Hou, Zong Liu; Han, Shen; Meng, Mingyao; Shi, Jianlin; Zhang, Yayong; Wang, Yi; Niu, Zhaoyi; Xie, Yanhua; Xiao, Benshan; Wang, Yuanfei; Li, Xiao; Yang, Lirong; Wang, Wenju; Jiang, Lihong

2018-03-05

BACKGROUND Recently, mutations in several genes have been described to be associated with sporadic ASD, but some genetic variants remain to be identified. The aim of this study was to use whole-exome sequencing (WES) combined with bioinformatics analysis to identify novel genetic variants in cases of sporadic congenital ASD, followed by validation by Sanger sequencing. MATERIAL AND METHODS Five Han patients with secundum ASD were recruited, and their tissue samples were analyzed by WES, followed by verification by Sanger sequencing of tissue and blood samples. Further evaluation using blood samples included 452 additional patients with sporadic secundum ASD (212 male and 240 female patients) and 519 healthy subjects (252 male and 267 female subjects) for further verification by a multiplexed MassARRAY system. Bioinformatic analyses were performed to identify novel genetic variants associated with sporadic ASD. RESULTS From five patients with sporadic ASD, a total of 181,762 genomic variants in 33 exon loci, validated by Sanger sequencing, were selected and underwent MassARRAY analysis in 452 patients with ASD and 519 healthy subjects. Three loci with high mutation frequencies, the 138665410 FOXL2 gene variant, the 23862952 MYH6 gene variant, and the 71098693 HYDIN gene variant were found to be significantly associated with sporadic ASD (PASD (PASD, and supported the use of WES and bioinformatics analysis to identify disease-associated mutations.

A clinically driven variant prioritization framework outperforms purely computational approaches for the diagnostic analysis of singleton WES data.

Science.gov (United States)

Stark, Zornitza; Dashnow, Harriet; Lunke, Sebastian; Tan, Tiong Y; Yeung, Alison; Sadedin, Simon; Thorne, Natalie; Macciocca, Ivan; Gaff, Clara; Oshlack, Alicia; White, Susan M; James, Paul A

2017-11-01

Rapid identification of clinically significant variants is key to the successful application of next generation sequencing technologies in clinical practice. The Melbourne Genomics Health Alliance (MGHA) variant prioritization framework employs a gene prioritization index based on clinician-generated a priori gene lists, and a variant prioritization index (VPI) based on rarity, conservation and protein effect. We used data from 80 patients who underwent singleton whole exome sequencing (WES) to test the ability of the framework to rank causative variants highly, and compared it against the performance of other gene and variant prioritization tools. Causative variants were identified in 59 of the patients. Using the MGHA prioritization framework the average rank of the causative variant was 2.24, with 76% ranked as the top priority variant, and 90% ranked within the top five. Using clinician-generated gene lists resulted in ranking causative variants an average of 8.2 positions higher than prioritization based on variant properties alone. This clinically driven prioritization approach significantly outperformed purely computational tools, placing a greater proportion of causative variants top or in the top 5 (permutation P-value=0.001). Clinicians included 40 of the 49 WES diagnoses in their a priori list of differential diagnoses (81%). The lists generated by PhenoTips and Phenomizer contained 14 (29%) and 18 (37%) of these diagnoses respectively. These results highlight the benefits of clinically led variant prioritization in increasing the efficiency of singleton WES data analysis and have important implications for developing models for the funding and delivery of genomic services.

Clinical Application of the PES/WES Index on Natural Teeth: Case Report and Literature Review

OpenAIRE

Lanza, Alessandro; Di Francesco, Fabrizio; De Marco, Gennaro; Femiano, Felice; Itro, Angelo

2017-01-01

The use of reliable indices to evaluate the aesthetic outcomes in the aesthetic area is an important and objective clinical aid to monitor the results over time. According to the literature various indices were proposed to evaluate aesthetic outcomes of implant-prosthetic rehabilitation of the anterior area like Peri-Implant and Crown Index [PICI], Implant Crown Aesthetic Index [ICAI], Pink Esthetic Score/White Esthetic Score [PES/WES], and Pink Esthetic Score [PES] but none of them was relat...

O design de produção nos filmes de Wes Anderson

OpenAIRE

Cunha, Humberto Thimoteo

2009-01-01

Esse projeto pesquisa a relação entre design e cinema, seguindo a linha do design de produção, o estudo da escolha de locações, a disposição de cenários, móveis e objetos. Posteriormente faz uma análise dos filmes do diretor Wes Anderson, buscando a importância dessa atividade no processo de produção dos filmes, analisando elementos de design de produção como objetos cenários e móveis, também elementos de figurino e elementos de pós-produção. A ánalise buscará mostrar que a importância do...

Oration " Pius et misericors " of Pope Pius II (Spring, 1459, Siena). Ed. and transl. by Michael von Cotta-Schönberg

OpenAIRE

Cotta-Schønberg, Michael

2015-01-01

In the spring of 1459, during a prolonged stay in Siena, Pope Pius II received a number of embassies from the rulers of Europe declaring obedience to the Apostolic See and to the new pope on behalf of their lord. One of the embassies was from Juan II, King of Aragon and Sicily. In his short reply to the oration of the ambassadors, the pope touched upon four themes: supremacy of the Roman Church; his own unworthiness for the exalted office; merits of the king and his House; benevolence of pope...

Use of capillary Western immunoassay (Wes) for quantification of dystrophin levels in skeletal muscle of healthy controls and individuals with Becker and Duchenne muscular dystrophy.

Science.gov (United States)

Beekman, Chantal; Janson, Anneke A; Baghat, Aabed; van Deutekom, Judith C; Datson, Nicole A

2018-01-01

Duchenne muscular dystrophy (DMD) is a neuromuscular disease characterized by progressive weakness of the skeletal and cardiac muscles. This X-linked disorder is caused by open reading frame disrupting mutations in the DMD gene, resulting in strong reduction or complete absence of dystrophin protein. In order to use dystrophin as a supportive or even surrogate biomarker in clinical studies on investigational drugs aiming at correcting the primary cause of the disease, the ability to reliably quantify dystrophin expression in muscle biopsies of DMD patients pre- and post-treatment is essential. Here we demonstrate the application of the ProteinSimple capillary immunoassay (Wes) method, a gel- and blot-free method requiring less sample, antibody and time to run than conventional Western blot assay. We optimized dystrophin quantification by Wes using 2 different antibodies and found it to be highly sensitive, reproducible and quantitative over a large dynamic range. Using a healthy control muscle sample as a reference and α-actinin as a protein loading/muscle content control, a panel of skeletal muscle samples consisting of 31 healthy controls, 25 Becker Muscle dystrophy (BMD) and 17 DMD samples was subjected to Wes analysis. In healthy controls dystrophin levels varied 3 to 5-fold between the highest and lowest muscle samples, with the reference sample representing the average of all 31 samples. In BMD muscle samples dystrophin levels ranged from 10% to 90%, with an average of 33% of the healthy muscle average, while for the DMD samples the average dystrophin level was 1.3%, ranging from 0.7% to 7% of the healthy muscle average. In conclusion, Wes is a suitable, efficient and reliable method for quantification of dystrophin expression as a biomarker in DMD clinical drug development.

Wes Jackson. In nature's way.

Science.gov (United States)

1992-09-01

The opinions and a biographical sketch of Wes Jackson, the founder of the Land Institute, are presented. The land Institute near Salina, Kansas is a nonprofit organization devoted to sustainable agriculture. Opinions are provided on the relationship of the Land Institute to sustainable agriculture, the definition of sustainability, the feasibility of replication of his work, his ideas about the destruction wreaked by the plow vs. the sword, technology and population growth, the future farmer, and the speed with which modern science has destroyed the ozone layer. Sustainable agriculture is using the prairie to provide answers to how agriculture can work with nature; the approach will take longer but will sustain both agriculture and people for another 10,000 years. The system runs on sunlight and recycles all materials and is based on the principles of ecosystems, which have been around for hundreds of years. Agricultural technology is based on a fossil fuel intensive infrastructure and is "parachuted into Third World countries." "Corn - the gift of the gods has been the killer of this continent." 50% of the topsoil has been lost, and soil is more important than oil. Advances in biotechnology are seen as the "human cleverness" approach; the preference is for an ecological approach first. Biotechnology tells how to "spin wheels faster," but it also generates more waste. The future farmer is more like the 19th century British naturalist. A projection is that 1st the oil is used up, then the natural gas, and when nuclear power is embraced, Murphy's Law must be repealed. It is important to understand the "we can'ts". Realization of limits will direct energy to the sun's potential and recycling and the flow of energy. Descartes' notion of correctable ignorance must be repudiated. Our knowledge-based world has led to acid rain, global warming, the ozone hole, and Chernobyl. It took just 25 years for chlorofluorocarbons to destroy the ozone layer. A philosophical shift in

Wes Andersons färgstarka värld : En studie av färg i film

OpenAIRE

Hallenquist, Peter

2009-01-01

  Abstract The focus of this essay is the american director Wes Anderson and the use of colour in his films. I also put some focus on colour as a neglected element in film studies, and what has caused this neglect. In my own research, I have analysed three of Anderson's films: Bottle Rocket (1996), The Royal Tenenbaums (2001) and The Darjeeling Limited (2007). To get a broad sense of a films use of colour, I have investigated the colour scheme, the colours of the costumes, as well as colour p...

Web-based Weather Expert System (WES) for Space Shuttle Launch

Science.gov (United States)

Bardina, Jorge E.; Rajkumar, T.

2003-01-01

The Web-based Weather Expert System (WES) is a critical module of the Virtual Test Bed development to support 'go/no go' decisions for Space Shuttle operations in the Intelligent Launch and Range Operations program of NASA. The weather rules characterize certain aspects of the environment related to the launching or landing site, the time of the day or night, the pad or runway conditions, the mission durations, the runway equipment and landing type. Expert system rules are derived from weather contingency rules, which were developed over years by NASA. Backward chaining, a goal-directed inference method is adopted, because a particular consequence or goal clause is evaluated first, and then chained backward through the rules. Once a rule is satisfied or true, then that particular rule is fired and the decision is expressed. The expert system is continuously verifying the rules against the past one-hour weather conditions and the decisions are made. The normal procedure of operations requires a formal pre-launch weather briefing held on Launch minus 1 day, which is a specific weather briefing for all areas of Space Shuttle launch operations. In this paper, the Web-based Weather Expert System of the Intelligent Launch and range Operations program is presented.

La sacralització del territori en l’oratòria del barroc valencià

Directory of Open Access Journals (Sweden)

Antoni López Quiles

2013-06-01

Full Text Available Resum: El sermó barroc és una proposta de comprensió del món, el qual era considerat com un enigma a desxifrar. Per a donar explicació d’aquells enigmes, els predicadors desenvoluparan les homilies d’acord amb uns esquemes d’elaboració molt rígids que intenten donar resposta a la triple exigència que tenia la retòrica tradicional de docere, flectere et delectare, i que recolzen en tots els recursos literaris al seu abast. A partir de l’esforç d’explicar el món, l’orador àulic del barroc insistirà en la idea de sacralitzar els ambients vitals, tant el lloc com el temps. L’article dóna raó d’eixe intent sacralitzador de la vida, concretat, en aquest cas, a l’espai viscut.Paraules clau: Oratòria sagrada, Sermons, Barroc, Sacralització del territoriAbstract: The baroque sermon is a way of comprehension of the world, which was considered to be a enigma to deciphering. To give an explanation of those enigmas, the preachers will develop the homilies following very rigid schemes trying to give response to the triple exigency that the traditional rhetoric had of docere, flectere te delectare, and that they make it rest on all the literary resources to their reach. From the effort to explain the world, the baroque aulic speaker will insist on the idea of sanctifying vital environments, both the place and the time. The article gives an account of this sanctified attempt of the life, embodied in this case, in the lived space.Keywords: Sacred Oratory, Sermons, Baroque, Sanctify the territory

23rd May 2011 - University of Liverpool Pro-Vice-Chancellor and Public Orator K. Everest (UK) Mrs Everest in the ATLAS visitor centre with Collaboration Deputy Spokesperson D. Charlton, in LHCb surface building with Collaboration Spokesperson A. Golutvin, accompanied throughout by P. Wells and Liverpool University T. Bowcock and M. Klein.

CERN Multimedia

Maximilen Brice

2011-01-01

23rd May 2011 - University of Liverpool Pro-Vice-Chancellor and Public Orator K. Everest (UK) Mrs Everest in the ATLAS visitor centre with Collaboration Deputy Spokesperson D. Charlton, in LHCb surface building with Collaboration Spokesperson A. Golutvin, accompanied throughout by P. Wells and Liverpool University T. Bowcock and M. Klein.

Complex Binding of the FabR Repressor of Bacterial Unsaturated Fatty Acid Biosynthesis to its Cognate Promoters

OpenAIRE

Feng, Youjun; Cronan, John E.

2011-01-01

Two transcriptional regulators, the FadR activator and the FabR repressor control biosynthesis of unsaturated fatty acids in Escherichia coli. FabR represses expression of the two genes, fabA and fabB, required for unsaturated fatty acid synthesis and has been reported to require the presence of an unsaturated thioester (of either acyl carrier protein or CoA) in order to bind the fabA and fabB promoters in vitro. We report in vivo experiments in which unsaturated fatty acid synthesis was bloc...

Chemical and laboratory analyses oceanographic data collected aboard the Wes Bordelon in the Gulf of Mexico from 2010-08-18 to 2010-08-22 in response to the Deepwater Horizon Oil Spill event (NODC Accession 0074863)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Chemical and laboratory analyses oceanographic data were collected aboard the Wes Bordelon in the Gulf of Mexico from 2010-08-18 to 2010-08-22 in response to the...

Chemical and physical oceanographic profile data collected from CTD casts aboard the Wes Bordelon in the Gulf of Mexico from 2010-09-05 to 2010-09-13 in response to the Deepwater Horizon oil spill event (NODC Accession 0069085)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Chemical and physical oceanographic profile data were collected aboard the Wes Bordelon in the Gulf of Mexico from 2010-09-05 to 2010-09-13 in response to the...

Chemical and physical oceanographic profile data collected from CTD casts aboard the Wes Bordelon in the Gulf of Mexico from 2010-08-18 to 2010-08-22 in response to the Deepwater Horizon oil spill event (NODC Accession 0069086)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Chemical and physical oceanographic profile data were collected aboard the Wes Bordelon in the Gulf of Mexico from 2010-08-18 to 2010-08-22 in response to the...

The Importance of Being ‘On the Road’: A Reading of the Journey in The Darjeeling Limited (2007 by Wes Anderson

Directory of Open Access Journals (Sweden)

José Duarte

2015-06-01

Full Text Available Road stories are significant cultural objects that “provide a ready space for [the] exploration” (Cohan and Hark 1997, 2 of different landscapes, contributing to the encounter of the traveller with him/herself or with the Other. These cultural encounters offer the opportunity both for inner reflection upon the nation in which the protagonists travel. Such is the case of the Whitman brothers in The Darjeeling Limited (2007, Wes Anderson, who embark on a journey in India, seeking spiritual enlightenment from the problems of the past. The confrontation with the foreign Other will not only put into perspective a changed notion of the Indian nation but also their true purpose in life. Based upon the idea of the transformative power of journeys, and considering The Darjeeling Limited as a road movie, this article analyzes the brothers’ awakening as they travel deeper into the Indian landscape to emerge with a renewed sense of self.

Cicerone e l’oratore tinctus litteris (de orat. 2,85: questioni testuali e stilistiche

Directory of Open Access Journals (Sweden)

Francesca Boldrer

2017-05-01

diminished its meaning to that “of an average or poor culture”, whereas it most probably indicates quite the contrary, as it reflects the widespread but prosaic synonym imbutus litteris. In addition, the word tinctus seems to allude to Lucretius – a poet (well known by Cicero that often uses tingo – and constitutes a positive and refined colour metaphor. In summary, the orator tinctus litteris, little appreciated by Antonius but still welcomed at his school, seems to be the portrait of the young Cicero, who really had been his student, a literate scholar committed for life to the ennoblement of the oratory style to a greater extent than his masters.

"Half a Century of Evolution of Neonatology: A Witness's Story" : Dr. K. C. Chaudhuri Lifetime Achievement Award Oration Delivered at AIIMS, New Delhi on 7th September 2014.

Science.gov (United States)

Vidyasagar, Dharmapuri

2015-12-01

Lifetime achievement awards are awarded to recognize contributions during the career of an individual, rather than for a single or multiple contributions of a person in his/her field of specialty. I am highly honored being the recipient of the Dr. K. C. Chaudhuri Lifetime Achiement Award Oration. The award for me is significant for several reasons: First being associated with legendary figure such as Dr. Chaudhuri, secondly being recognized by my fellow Indian colleagues. Finally, it also marks half a century of my experience in development of subspecialty of neonatology in US. Some fifty and odd years ago, as an young novice from India I joined the mainstream of this evolution, thanks to my professors and mentors in US and thanks to America, the land of opportunity. During this odyssey, I met many great men and women of science and intellect, saw great scientific discoveries, many innovations, combined with social changes that led to significant reduction of neonatal mortality rates in the industrialized Western countries. I also saw the "Globalization" of "Modern Neonatology" in which I participated with vigor; thus, improving the newborn care in four corners of the world. I am proud that I had the opportunity to contribute a little to growth of neonatology in US and outside the US. This is the story of my professional life. The message of my life story for the younger generation is : Dream big, never give up your dreams. Hardwork, maintaining your integrity, and honesty are the three precepts that will define your character and you will be rewarded in the long run.

Establishing very long-chain fatty alcohol and wax ester biosynthesis in Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Wenning, Leonie; Yu, Tao; David, Florian

2017-01-01

used WEs are mainly isolated from Simmondsia chinensis (jojoba), but the high extraction costs and limited harvest areas constrain their use. The use of FARs in combination with different WSs to achieve a synthesis of jojoba-like WEs in bacteria and yeast has been reported previously, but the products...... were restricted to C28-C36 WEs. These rather short WEs make up only a very small percentage of the total WEs in natural jojoba oil. The synthesis of longer chain WEs (up to C44) in Saccharomyces cerevisiae has so far only been achieved after substrate feeding. Here we identified new routes......, respectively, after 48h. Moreover, we enabled the synthesis of jojoba-like WEs up to a chain length of C42, catalyzed by a combination of Maqu_2220 together with the WS from S. chinensis (SciWS) and the S. cerevisiae elongase Elo2p, with a maximum yield of 12.24±3.35mg/g CDW after 48h....

Wind Energy Solutions : to bring renewable energy everywhere

International Nuclear Information System (INIS)

Baigent, K.

2006-01-01

This presentation provided details of Wind Energy Solutions (WES) Canada's current activities and research innovations. Established initially in Holland in 2004, WES Canada's corporate activities include technology development; licensing, registration and approvals; product development; manufacturing and distribution; and global service and maintenance training. WES Canada is the exclusive importer of WES turbines for Canada and the United States, and offers turnkey wind energy solutions for local dealers and installers. WES product technology aims to provide flexible logistics, as well as to facilitate local production and project development. WES turbines range from 2.5 kW to 250 KW and are available for both on-site power generation and grid-connected applications. The presentation provided specifications for the WES 5 Tulipo wind turbine, a low noise level, low vibration turbine that provides 2 independent safety systems: a failsafe brake on fast shaft of gear; and emergency yawing. A series of photographs demonstrated the installation process of the Tulipo. It was noted that many WES turbines are used in farming applications, as the turbine fits easily on 1 truck, and is easy to install with a foundation made by a local contractor using WES technical drawings engineered for local soil conditions. The turbine is also suitable for factories, harbours, schools and remote villages. It was concluded that the turbines have been specifically engineered for cold climates, as an imbalance control will prevent operation when the blades have significant ice build-up. refs., tabs., figs

The clinical utility of whole-exome sequencing in the context of rare diseases - the changing tides of medical practice.

Science.gov (United States)

Nguyen, M T; Charlebois, K

2015-10-01

Whole-exome sequencing (WES) carries the potential to facilitate the identification of disease causing genes. This is particularly relevant concerning rare diseases, which proves particularly difficult for physicians to diagnose. However, the complexity of this technology renders its applicability onto the clinical setting uncertain. Our study thus aims to understand physicians' perspectives regarding the clinical utility of WES, particularly for providing a diagnosis for patients with rare diseases. Ten semi-structured interviews were conducted with physicians with experience and familiarity with WES, and the major themes that emerged from our interviews were (i) the relevance of WES in diagnosing patients with rare diseases (appropriateness); (ii) the cost-effectiveness of WES (accessibility), (iii) the practical issues related to the clinical implementation of WES (practicability); and (iv) ethical, legal and social issues (acceptability). Our study highlights how the clinical implementation of WES presents additional challenges where rare diseases are taken into consideration. © 2014 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Rahima Dawood Oration

African Journals Online (AJOL)

2001-12-05

colonial world is the retention of the colonial power structure, the other .... The children and the grandchildren of the establishment are not willing to follow in the footsteps of the leadership. This is noticeable in politics, in.

Ceremony 4 : academic oration

OpenAIRE

Sultana, Mark

2012-01-01

Questions like ‘What is the university?’ ‘What is its role?’ are typical philosophical questions. They are characteristically huge questions. But they are queries which engage us continuously. They are important questions. They were asked by a long line of distinguished thinkers who gave variant, yet overlapping, answers: universities should be governed by “an idea of reason” (Immanuel Kant); they serve the culture of the nation-state (Wilhelm von Humboldt); they exist to “civilise gentlemen”...

Looking beyond the exome: a phenotype-first approach to molecular diagnostic resolution in rare and undiagnosed diseases

Science.gov (United States)

Pena, Loren DM; Jiang, Yong-Hui; Schoch, Kelly; Spillmann, Rebecca C.; Walley, Nicole; Stong, Nicholas; Horn, Sarah Rapisardo; Sullivan, Jennifer A.; McConkie-Rosell, Allyn; Kansagra, Sujay; Smith, Edward C.; El-Dairi, Mays; Bellet, Jane; Ann Keels, Martha; Jasien, Joan; Kranz, Peter G.; Noel, Richard; Nagaraj, Shashi K.; Lark, Robert K.; Wechsler, Daniel SG; del Gaudio, Daniela; Leung, Marco L.; Hendon, Laura G.; Parker, Collette C.; Jones, Kelly L.; Goldstein, David B.; Shashi, Vandana

2017-01-01

Purpose To describe examples of missed pathogenic variants on whole exome sequencing (WES) and the importance of deep phenotyping for further diagnostic testing. Methods Guided by phenotypic information, three children with negative WES underwent targeted single gene testing. Results Individual 1 had a clinical diagnosis consistent with infantile systemic hyalinosis, although WES and an NGS-based ANTXR2 test were negative. Sanger sequencing of ANTXR2 revealed a homozygous single base pair insertion, previously missed by the WES variant caller software. Individual 2 had neurodevelopmental regression and cerebellar atrophy, with no diagnosis on WES. New clinical findings prompted Sanger sequencing and copy number testing of PLA2G6. A novel homozygous deletion of the non-coding exon 1 (not included in the WES capture kit) was detected, with extension into the promoter, confirming the clinical suspicion of infantile neuroaxonal dystrophy. Individual 3 had progressive ataxia, spasticity and MRI changes of vanishing white matter leukoencephalopathy. An NGS leukodystrophy gene panel and WES showed a heterozygous pathogenic variant in EIF2B5; no deletions/duplications were detected. Sanger sequencing of EIF2B5 showed a frameshift indel, likely missed due to failure of alignment. Conclusions These cases illustrate potential pitfalls of WES/NGS testing, and the importance of phenotype-guided molecular testing in yielding diagnoses. PMID:28914269

A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology.

Science.gov (United States)

Vissers, Lisenka E L M; van Nimwegen, Kirsten J M; Schieving, Jolanda H; Kamsteeg, Erik-Jan; Kleefstra, Tjitske; Yntema, Helger G; Pfundt, Rolph; van der Wilt, Gert Jan; Krabbenborg, Lotte; Brunner, Han G; van der Burg, Simone; Grutters, Janneke; Veltman, Joris A; Willemsen, Michèl A A P

2017-09-01

Implementation of novel genetic diagnostic tests is generally driven by technological advances because they promise shorter turnaround times and/or higher diagnostic yields. Other aspects, including impact on clinical management or cost-effectiveness, are often not assessed in detail prior to implementation. We studied the clinical utility of whole-exome sequencing (WES) in complex pediatric neurology in terms of diagnostic yield and costs. We analyzed 150 patients (and their parents) presenting with complex neurological disorders of suspected genetic origin. In a parallel study, all patients received both the standard diagnostic workup (e.g., cerebral imaging, muscle biopsies or lumbar punctures, and sequential gene-by-gene-based testing) and WES simultaneously. Our unique study design allowed direct comparison of diagnostic yield of both trajectories and provided insight into the economic implications of implementing WES in this diagnostic trajectory. We showed that WES identified significantly more conclusive diagnoses (29.3%) than the standard care pathway (7.3%) without incurring higher costs. Exploratory analysis of WES as a first-tier diagnostic test indicates that WES may even be cost-saving, depending on the extent of other tests being omitted. Our data support such a use of WES in pediatric neurology for disorders of presumed genetic origin.Genet Med advance online publication 23 March 2017.

Accommodating World Englishes in Developing EFL Learners' Oral Communication

Science.gov (United States)

Mukminatien, Nur

2012-01-01

This article aims to discuss issues of World Englishes (WEs) and the implications in ELT. It explores the extent to which WEs are taken into account as emerging English varieties different from inner circle varieties, how WEs should be accommodated by English teachers, and which standard to adopt to accommodate learner's linguistic needs for…

Example-Based Learning: Effects of Different Types of Examples on Student Performance, Cognitive Load and Self-Efficacy in a Statistical Learning Task

Science.gov (United States)

Huang, Xiaoxia

2017-01-01

Previous research has indicated the disconnect between example-based research focusing on worked examples (WEs) and that focusing on modeling examples. The purpose of this study was to examine and compare the effect of four different types of examples from the two separate lines of research, including standard WEs, erroneous WEs, expert (masterly)…

The Future of World Englishes in Language Testing

Science.gov (United States)

Brown, James Dean

2014-01-01

This article begins by defining "world Englishes" (WEs) and the related paradigm of inner-, outer-, and expanding-circle English(es). The discussion then turns to the central concerns of the WEs and language testing (LT) communities with regard to how English tests can best be constructed to include various WEs by discussing (a) what…

Designing Efficient Self-Diagnosis Activities in the Physics Classroom

Science.gov (United States)

Safadi, Rafi'

2017-12-01

Self-diagnosis (SD) activities require students to self-diagnose their solutions to problems that they solved on their own. This involves identifying where they went wrong and then explaining the nature of their errors—why they went wrong—aided by some form of support. Worked examples (WEs) are often used to support students in SD activities. A WE is a step-by-step demonstration of how to solve a problem. One unresolved issue is why students fail to exploit WEs in SD exercises. Yerushalmi et al., for instance, provided students with written WEs and asked them to self-diagnose their solutions with respect to these WEs. These authors found no correlation between students' SD performance and their subsequent problem-solving performance on transfer problems, suggesting that students had only superficially exploited the written WEs. The aim of this article is to describe a new SD activity that was developed to prompt students to effectively use written WEs when self-diagnosing, and to examine its effectiveness in advancing students' learning in physics.

Reporting results from whole-genome and whole-exome sequencing in clinical practice: a proposal for Canada?

Science.gov (United States)

Zawati, Ma'n H; Parry, David; Thorogood, Adrian; Nguyen, Minh Thu; Boycott, Kym M; Rosenblatt, David; Knoppers, Bartha Maria

2014-01-01

This article proposes recommendations for the use of whole-genome and whole-exome (WGS/WES) sequencing in clinical practice, endorsed by the board of directors of the Canadian College of Medical Geneticists. The publication of statements and recommendations by several international and national organisations on clinical WGS/WES has prompted a need for Canadian-specific guidance. A multi-disciplinary group consisting of lawyers, ethicists, genetic researchers, and clinical geneticists was assembled to review existing guidelines on WGS/WES and identify provisions relevant to the Canadian context. Definitions were provided to orient the recommendations and to minimize confusion with other recommendations. Recommendations include the following: WGS/WES should be used in a judicious and cost-efficient manner; WGS/WES should be used to answer a clinical question; and physicians need to explain to adult patients the nature of the results that could arise, so as to allow them to make informed choices over whether to take the test and which results they wish to receive. Recommendations are also provided for WGS/WES in the pediatric context, and for when results implicate patients' family members. These recommendations are only a proposal to be developed into comprehensive Canadian-based guidelines. They aim to promote discussion about the reporting of WGS/WES results, and to encourage the ethical implementation of these new technologies in the clinical setting.

Lynch syndrome patients' views of and preferences for return of results following whole exome sequencing.

Science.gov (United States)

Hitch, Kelly; Joseph, Galen; Guiltinan, Jenna; Kianmahd, Jessica; Youngblom, Janey; Blanco, Amie

2014-08-01

Whole exome sequencing (WES) uses next generation sequencing technology to provide information on nearly all functional, protein-coding regions in an individual's genome. Due to the vast amount of information and incidental findings that can be generated from this technology, patient preferences must be investigated to help clinicians consent and return results to patients. Patients (n = 19) who were previously clinically diagnosed with Lynch syndrome, but received uninformative negative Lynch syndrome genetic results through traditional molecular testing methods participated in semi-structured interviews after WES testing but before return of results to explore their views of WES and preferences for return of results. Analyses of interview results found that nearly all participants believed that the benefits of receiving all possible results generated from WES outweighed the undesirable effects. The majority of participants conveyed that relative to coping with a cancer diagnosis, information generated from WES would be manageable. Importantly, participants' experience with Lynch syndrome influenced their notions of genetic determinism, tolerance for uncertain results, and family communication plans. Participants would prefer to receive WES results in person from a genetic counselor or medical geneticist so that an expert could help explain the meaning and implications of the potentially large quantity and range of complicated results. These results underscore the need to study various populations with regard to the clinical use of WES in order to effectively and empathetically communicate the possible implications of this new technology and return results.

Establishing very long-chain fatty alcohol and wax ester biosynthesis in Saccharomyces cerevisiae.

Science.gov (United States)

Wenning, Leonie; Yu, Tao; David, Florian; Nielsen, Jens; Siewers, Verena

2017-05-01

Wax esters (WEs) are neutral lipids and can be used for a broad range of commercial applications, including personal care products, lubricants, or coatings. They are synthesized by enzymatic reactions catalyzed by a fatty acyl reductase (FAR) and a wax ester synthase (WS). At present, commercially used WEs are mainly isolated from Simmondsia chinensis (jojoba), but the high extraction costs and limited harvest areas constrain their use. The use of FARs in combination with different WSs to achieve a synthesis of jojoba-like WEs in bacteria and yeast has been reported previously, but the products were restricted to C28-C36 WEs. These rather short WEs make up only a very small percentage of the total WEs in natural jojoba oil. The synthesis of longer chain WEs (up to C44) in Saccharomyces cerevisiae has so far only been achieved after substrate feeding. Here we identified new routes for producing very long-chain fatty alcohols (VLCFOHs) up to a chain length of C22 by heterologous expression of a FAR derived from Apis mellifera (AmFAR1) or Marinobacter aquaeolei VT8 (Maqu_2220) in S. cerevisiae and achieved maximum yields of 3.22 ± 0.36 mg/g cell dry weight (CDW) and 7.84 ± 3.09 mg/g CDW, respectively, after 48 h. Moreover, we enabled the synthesis of jojoba-like WEs up to a chain length of C42, catalyzed by a combination of Maqu_2220 together with the WS from S. chinensis (SciWS) and the S. cerevisiae elongase Elo2p, with a maximum yield of 12.24 ± 3.35 mg/g CDW after 48 h. Biotechnol. Bioeng. 2017;114: 1025-1035. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders.

Science.gov (United States)

Stark, Zornitza; Tan, Tiong Y; Chong, Belinda; Brett, Gemma R; Yap, Patrick; Walsh, Maie; Yeung, Alison; Peters, Heidi; Mordaunt, Dylan; Cowie, Shannon; Amor, David J; Savarirayan, Ravi; McGillivray, George; Downie, Lilian; Ekert, Paul G; Theda, Christiane; James, Paul A; Yaplito-Lee, Joy; Ryan, Monique M; Leventer, Richard J; Creed, Emma; Macciocca, Ivan; Bell, Katrina M; Oshlack, Alicia; Sadedin, Simon; Georgeson, Peter; Anderson, Charlotte; Thorne, Natalie; Melbourne Genomics Health Alliance; Gaff, Clara; White, Susan M

2016-11-01

To prospectively evaluate the diagnostic and clinical utility of singleton whole-exome sequencing (WES) as a first-tier test in infants with suspected monogenic disease. Singleton WES was performed as a first-tier sequencing test in infants recruited from a single pediatric tertiary center. This occurred in parallel with standard investigations, including single- or multigene panel sequencing when clinically indicated. The diagnosis rate, clinical utility, and impact on management of singleton WES were evaluated. Of 80 enrolled infants, 46 received a molecular genetic diagnosis through singleton WES (57.5%) compared with 11 (13.75%) who underwent standard investigations in the same patient group. Clinical management changed following exome diagnosis in 15 of 46 diagnosed participants (32.6%). Twelve relatives received a genetic diagnosis following cascade testing, and 28 couples were identified as being at high risk of recurrence in future pregnancies. This prospective study provides strong evidence for increased diagnostic and clinical utility of singleton WES as a first-tier sequencing test for infants with a suspected monogenic disorder. Singleton WES outperformed standard care in terms of diagnosis rate and the benefits of a diagnosis, namely, impact on management of the child and clarification of reproductive risks for the extended family in a timely manner.Genet Med 18 11, 1090-1096.

Genetic counselors' views and experiences with the clinical integration of genome sequencing.

Science.gov (United States)

Machini, Kalotina; Douglas, Jessica; Braxton, Alicia; Tsipis, Judith; Kramer, Kate

2014-08-01

In recent years, new sequencing technologies known as next generation sequencing (NGS) have provided scientists the ability to rapidly sequence all known coding as well as non-coding sequences in the human genome. As the two emerging approaches, whole exome (WES) and whole genome (WGS) sequencing, have started to be integrated in the clinical arena, we sought to survey health care professionals who are likely to be involved in the implementation process now and/or in the future (e.g., genetic counselors, geneticists and nurse practitioners). Two hundred twenty-one genetic counselors- one third of whom currently offer WES/WGS-participated in an anonymous online survey. The aims of the survey were first, to identify barriers to the implementation of WES/WGS, as perceived by survey participants; second, to provide the first systematic report of current practices regarding the integration of WES/WGS in clinic and/or research across the US and Canada and to illuminate the roles and challenges of genetic counselors participating in this process; and third to evaluate the impact of WES/WGS on patient care. Our results showed that genetic counseling practices with respect to WES/WGS are consistent with the criteria set forth in the ACMG 2012 policy statement, which highlights indications for testing, reporting, and pre/post test considerations. Our respondents described challenges related to offering WES/WGS, which included billing issues, the duration and content of the consent process, result interpretation and disclosure of incidental findings and variants of unknown significance. In addition, respondents indicated that specialty area (i.e., prenatal and cancer), lack of clinical utility of WES/WGS and concerns about interpretation of test results were factors that prevented them from offering this technology to patients. Finally, study participants identified the aspects of their professional training which have been most beneficial in aiding with the integration of

Protein (Cyanobacteria): 493036452 [PGDBj - Ortholog DB

Lifescience Database Archive (English)

Full Text Available oration protein HypA Coleofasciculus chthonoplastes MHETDMTKALILTVRQWWEEQPSRPQIDTIH... WP_006104069.1 ... 1117:21745 ... 1150:63074 1301283:85471 ... 669368:4227 64178:4227 ... hydrogenase nickel incorp

Whole exome sequencing in neurogenetic odysseys: An effective, cost- and time-saving diagnostic approach.

Directory of Open Access Journals (Sweden)

Marta Córdoba

Full Text Available Diagnostic trajectories for neurogenetic disorders frequently require the use of considerable time and resources, exposing patients and families to so-called "diagnostic odysseys". Previous studies have provided strong evidence for increased diagnostic and clinical utility of whole-exome sequencing in medical genetics. However, specific reports assessing its utility in a setting such as ours- a neurogeneticist led academic group serving in a low-income country-are rare.To assess the diagnostic yield of WES in patients suspected of having a neurogenetic condition and explore the cost-effectiveness of its implementation in a research group located in an Argentinean public hospital.This is a prospective study of the clinical utility of WES in a series of 40 consecutive patients selected from a Neurogenetic Clinic of a tertiary Hospital in Argentina. We evaluated patients retrospectively for previous diagnostic trajectories. Diagnostic yield, clinical impact on management and economic diagnostic burden were evaluated.We demonstrated the clinical utility of Whole Exome Sequencing in our patient cohort, obtaining a diagnostic yield of 40% (95% CI, 24.8%-55.2% among a diverse group of neurological disorders. The average age at the time of WES was 23 (range 3-70. The mean time elapsed from symptom onset to WES was 11 years (range 3-42. The mean cost of the diagnostic workup prior to WES was USD 1646 (USD 1439 to 1853, which is 60% higher than WES cost in our center.WES for neurogenetics proved to be an effective, cost- and time-saving approach for the molecular diagnosis of this heterogeneous and complex group of patients.

Esthetic evaluation of maxillary single-tooth implants in the esthetic zone

Science.gov (United States)

Cho, Hae-Lyung; Lee, Jae-Kwan; Um, Heung-Sik

2010-01-01

Purpose The aim of this study is to assess the influence exerted by the observer's dental specialization and compare patients' opinion with observers' opinion of the esthetics of maxillary single-tooth implants in the esthetic zone. Methods Forty-one adult patients, who were treated with a single implant in the esthetic zone, were enrolled in this study. Eight observers (2 periodontists, 2 prosthodontists, 2 orthodontists and 2 senior dental students) applied the pink esthetic score (PES)/white esthetic score (WES) to 41 implant-supported single restorations twice with an interval of 4 weeks. We used a visual analog scale (VAS) to assess the patient's satisfaction with the treatment outcome from an esthetic point of view. Results In the PES/WES, very good and moderate intraobserver agreements were noted between the first and second rating. The mean total PES/WES was 11.19 ± 3.59. The mean PES was 5.17 ± 2.29 and mean WES was 6.02 ± 1.96. In the total PES/WES, the difference between the groups was not significant. However, in the WES, the difference between the groups was significant and prosthodontists were found to have assigned poorer ratings than the other groups. Periodontists gave higher ratings than prosthodontists and senior dental students. Orthodontists were clearly more critical than the other observers. The statistical analysis revealed statistically significant correlation between patients' esthetic perception and dentists' perception of the anterior tooth. However, the correlation between the total PES/WES and the VAS score for the first premolar was not statistically significant. Conclusions The PES/WES is an objective tool in rating the esthetics of implant supported single crowns and adjacent soft tissues. Orthodontists were the most critical observers, while periodontists were more generous than other observers. The statistical analysis revealed a statistically significant correlation between patients' esthetic perception and dentists

76 FR 34914 - Energy Conservation Program for Consumer Products and Certain Commercial and Industrial Equipment...

Science.gov (United States)

2011-06-15

... CONTACT: Mr. Wes Anderson, U.S. Department of Energy, Office of Energy Efficiency and Renewable Energy...: (202) 586-7335. E-mail: Wes.Anderson@ee.doe.gov . In the Office of General Counsel, contact Ms...

76 FR 30555 - Energy Conservation Program for Consumer Products: Test Procedures for Residential Central Air...

Science.gov (United States)

2011-05-26

[email protected] . FOR FURTHER INFORMATION CONTACT: Mr. Wes Anderson, U.S. Department of Energy, Office... Avenue, SW., Washington, DC 20585-0121. Telephone: (202) 586-7335. E-mail: Wes.Anderson@ee.doe.gov . Ms...

Æstet til sidste blodige krumme

DEFF Research Database (Denmark)

Schubart, Rikke

2014-01-01

Rikke Schubart interviewer instruktør Wes Anderson om hans nye film The Grand Budapest Hotel (2014)......Rikke Schubart interviewer instruktør Wes Anderson om hans nye film The Grand Budapest Hotel (2014)...

Identification of genetic defects in primary immunodeficiencies by whole exome sequencing

DEFF Research Database (Denmark)

Christiansen, Mette; Jensen, Jens Magnus Bernth; Veirum, Jens Erik

2014-01-01

to hypogammaglobulinaemia, and increased risk of both infections as well as cancer. We employed whole exome sequencing (WES) to identify mutations associated with primary immunodeficiency in severely affected children. We present WES data on 2 patients with severe immunodeficiency. WES was performed using TruSeq exome kit...... and severe infections including sepsis. Second, we identified compound heterozygote stopgain mutations in RAD52 and a heterozygote mutation in LRRC8A in a 7 year-old girl with T-cell deficiency, reduced T-cell mediated B-cell activity, hypogammaglobulinaemia, prolonged splenomegali and benign adenopathy. RAD......52 has not previously been linked to immunodeficiency and we are currently investigating the functional consequences. Knowledge of the mechanisms underlying immunodeficiencies is a prerequisite for understanding disease pathogenesis. WES allows the demonstration of immune defects that may result from...

Diagnostic Impact and Cost-effectiveness of Whole-Exome Sequencing for Ambulant Children With Suspected Monogenic Conditions.

Science.gov (United States)

Tan, Tiong Yang; Dillon, Oliver James; Stark, Zornitza; Schofield, Deborah; Alam, Khurshid; Shrestha, Rupendra; Chong, Belinda; Phelan, Dean; Brett, Gemma R; Creed, Emma; Jarmolowicz, Anna; Yap, Patrick; Walsh, Maie; Downie, Lilian; Amor, David J; Savarirayan, Ravi; McGillivray, George; Yeung, Alison; Peters, Heidi; Robertson, Susan J; Robinson, Aaron J; Macciocca, Ivan; Sadedin, Simon; Bell, Katrina; Oshlack, Alicia; Georgeson, Peter; Thorne, Natalie; Gaff, Clara; White, Susan M

2017-09-01

Optimal use of whole-exome sequencing (WES) in the pediatric setting requires an understanding of who should be considered for testing and when it should be performed to maximize clinical utility and cost-effectiveness. To investigate the impact of WES in sequencing-naive children suspected of having a monogenic disorder and evaluate its cost-effectiveness if WES had been available at different time points in their diagnostic trajectory. This prospective study was part of the Melbourne Genomics Health Alliance demonstration project. At the ambulatory outpatient clinics of the Victorian Clinical Genetics Services at the Royal Children's Hospital, Melbourne, Australia, children older than 2 years suspected of having a monogenic disorder were prospectively recruited from May 1 through November 30, 2015, by clinical geneticists after referral from general and subspecialist pediatricians. All children had nondiagnostic microarrays and no prior single-gene or panel sequencing. All children underwent singleton WES with targeted phenotype-driven analysis. The study examined the clinical utility of a molecular diagnosis and the cost-effectiveness of alternative diagnostic trajectories, depending on timing of WES. Of 61 children originally assessed, 44 (21 [48%] male and 23 [52%] female) aged 2 to 18 years (mean age at initial presentation, 28 months; range, 0-121 months) were recruited, and a diagnosis was achieved in 23 (52%) by singleton WES. The diagnoses were unexpected in 8 of 23 (35%), and clinical management was altered in 6 of 23 (26%). The mean duration of the diagnostic odyssey was 6 years, with each child having a mean of 19 tests and 4 clinical genetics and 4 nongenetics specialist consultations, and 26 (59%) underwent a procedure while under general anesthetic for diagnostic purposes. Economic analyses of the diagnostic trajectory identified that WES performed at initial tertiary presentation resulted in an incremental cost savings of A$9020 (US$6838) per

Developing and Implementing "Waupaca Eating Smart": A Restaurant and Supermarket Intervention to Promote Healthy Eating Through Changes in the Food Environment.

Science.gov (United States)

Escaron, Anne L; Martinez-Donate, Ana P; Riggall, Ann Josie; Meinen, Amy; Hall, Beverly; Nieto, F Javier; Nitzke, Susan

2016-03-01

Restaurants and food stores are suitable settings for healthy eating interventions. A community-academic partnership developed and implemented "Waupaca Eating Smart" (WES), a healthy eating program in restaurants and supermarkets of a rural, Midwest community. Previous interventions targeted either restaurants or small food stores nearly all in urban areas. Intervention design and implementation is rarely documented, making replication difficult for interested researchers and communities. In this article, we report the activities we undertook to develop and implement WES. Working with a local nutrition and activity coalition, we used evidence-based strategies guided by the social ecological model and social marketing principles to inform the content of WES. Formative assessment included a review of the literature, statewide key informant interviews and focus groups with restaurant and food store operators and patrons, a local community survey, and interviews with prospective WES businesses. WES was implemented in seven restaurants and two supermarkets and evaluated for feasibility and acceptance using surveys and direct observation of WES implementation. Prior to this intervention, only one of seven restaurants had three or more meals that met WES nutrition criteria. By the end of the program, 38 meals were labeled and promoted to restaurant customers, and the team had staffed four side salad taste tests for supermarket customers. Four and 10 months after intervention launch, the majority of the program's strategies were observed in participating outlets, suggesting that these program's strategies are feasible and can be sustained. Operators reported strong satisfaction overall. A combined restaurant- and supermarket-based healthy eating intervention is feasible and positively valued in rural communities. Further research is needed to better understand how to foster sustainability of these interventions and their impact on customer food choices. © 2015 Society for

HIV epidemic in South Africa: A comparison of HIV epidemic patterns of two extreme provinces in South Africa

Directory of Open Access Journals (Sweden)

Khangelani Zuma

2014-08-01

Agtergrond: Suid-Afrika ondervind een van die ergste MIV-epedemies, wat verskil ten opsigte van elke provinsie en distrik en binne elke provinise. Doelstelling: Om MIV-voorkoms en -patrone tussen twee provinises in Suid-Afrika te ondersoek en vergelyk. Metode: ‘Ken jou epidemie’ sintese dui daarop dat die voorkomssyfer van MIV in ouer ouderdomsgroepe styg en daal by jonger mense. Ons het sekondêre data analieses van bevolkingsgebaseerde en swangerskapsorg waarnemingsopnames (ANC gebruik om neigings en patrone in MIV-voorkoms in Kwa-Zulu Natal en die Wes-Kaap, vas te stel. Resultate: Ofskoon Kwa-Zulu Natal die hoogste voorkoms in Suid-Afrika (15.5% vergelyk met 3.8% in die Wes-Kaap het, is daar ‘n aansienlike onlangse afname (6% in die voorkoms van MIV in Kwa-Zulu Natal waargeneem, vergelyk met die 2% verhoging in die Wes-Kaap, gebasseer op ANC data, in jongmense in die ouderdomsgroep 15–24 jaar. Hierdie resultate is konsekwent met dié van die bevolkingsgebaseerde opname, waar ‘n afname van 0.3% in MIV-voorkoms in Kwa-Zulu Natal waargeneem is, vergelyk met ‘n toename van 0.7% in die jeug van die Wes-Kaap. Altwee die ANC-resultate en die bevolkings-gebaseerde opnames wat in verskillende jare uitgevoer is, wys ’n afname in MIV-voorkoms onder die jeug in Kwa-Zuly Natal vergelyk met ’n toename onder dieselfde ouderdomsgroep in die Wes-Kaap. MIV-infeksie onder hierdie ouderdomsgroep word verbind met ’n onlangse infeksie, wat ’n toename van die epidemie in die Wes-Kaap, vergelyk met Kwa-Zulu Natal aandui. Gevolgtrekkings: Ingryping, wat daarop gemik is om infeksies soos seksuele onthouding en die reklame van kondome vir hierdie ouderdomsgroep, behoort wyd in die Wes-Kaap geimplementeer te word. Hierdie behoort voorligtings- en toetsveldtogte in te sluit.

Differences in the Psychosocial Work Environment of Different Types of Schools.

Science.gov (United States)

Docker, John G.; And Others

1989-01-01

Discusses the use of the Work Environment Scale (WES) to measure teachers' perceptions of psychosocial dimensions of their school environment. Describes an application of WES in which work climates of different school types were compared and contrasted. (RJC)

De Novo Coding Variants Are Strongly Associated with Tourette Disorder

DEFF Research Database (Denmark)

Willsey, A Jeremy; Fernandez, Thomas V; Yu, Dongmei

2017-01-01

Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186 ...

Evaluation and comparison of health care Work Environment Scale in military settings.

Science.gov (United States)

Maloney, J P; Anderson, F D; Gladd, D L; Brown, D L; Hardy, M A

1996-05-01

The purpose of this study was to describe health care providers' perceptions of their work environment at a large U.S. Army medical center, and to compare the findings to other military medical centers. The sample (N = 112) consisted of the professional nursing staff working on the nine inpatient units. The Work Environmental Scale (WES) was used to measure perceptions of the workplace relative to gender, position (head nurses, staff nurses, and agency nurses), specialty nursing (intensive care unit [ICU] versus non-ICU), education (MSN, BSN, and ADN), and patterns of differences between the WES subscales of four military medical centers. Results of the study indicate that there were no significant gender differences. Head nurses, non-ICU nurses, and MSN nurses perceived their environment more positively. There were significant differences in the WES subscales between the military hospitals. Implications for nursing using the WES were recommended.

Evolution of dosimetric phantoms

International Nuclear Information System (INIS)

Reddy, A.R.

2010-01-01

In this oration evolution of the dosimetric phantoms for radiation protection and for medical use is briefly reviewed. Some details of the development of Indian Reference Phantom for internal dose estimation are also presented

Journal of Humanities - Vol 18, No 1 (2004)

African Journals Online (AJOL)

Gorgias' scepticism regarding Greek social class distinctions in the Funeral Oration (DK.82.BSa) · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Victor S. Alumona, 1-11 ...

75 FR 27227 - Energy Conservation Program: Energy Conservation Standards for Residential Central Air...

Science.gov (United States)

2010-05-14

...-7335. E-mail: Wes.Anderson@ee.doe.gov . Ms. Elizabeth Kohl, U.S. Department of Energy, Office of the... additional information regarding visiting the Resource Room. FOR FURTHER INFORMATION CONTACT: Mr. Wes Anderson, U.S. Department of Energy, Office of Energy Efficiency and Renewable Energy, Building...

Esthetic outcome for maxillary anterior single implants assessed by different dental specialists.

Science.gov (United States)

Al-Dosari, Abdullah; Al-Rowis, Ra'ed; Moslem, Feras; Alshehri, Fahad; Ballo, Ahmed M

2016-10-01

The aim of this study was to assess the esthetic outcome of maxillary anterior single implants by comparing the esthetic perception of dental professionals and patients. Twenty-three patients with single implants in the esthetic zone were enrolled in this study. Dentists of four different dental specialties (Three orthodontists, three oral surgeons, three prosthodontists, and three periodontists) evaluated the pink esthetic score (PES)/white esthetic score (WES) for 23 implant-supported single restorations. The satisfactions of the patients on the esthetic outcome of the treatment have been evaluated according to the visual analog scale (VAS). The mean total PES/WES was 12.26 ± 4.76. The mean PES was 6.45 ± 2.78 and mean WES was 5.80 ± 2.82. There was a statistically significant difference among the different specialties for WES ( P esthetic perception, thereby providing rationales for involving patients in the treatment plan to achieve higher levels of patient satisfaction.

Analysis of wax esters by silver-ion high-performance liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Vrkoslav, Vladimír; Urbanová, Klára; Háková, Matina; Cvačka, Josef

2013-08-09

Wax esters (WEs), esters of long-chain fatty acids and long-chain alcohols, were analysed by Ag-HPLC/APCI-MS/MS. Two ChromSpher Lipids columns connected in series (a total length of 50cm) and hexane-2-propanol-acetonitrile mobile phases were used to achieve good separation of the molecular species. The chromatographic behaviour of WEs was studied under optimised conditions: retention increased with the number of double bonds and with the temperature (15-35°C); retention times were affected by the double-bond position, trans isomers eluted earlier than cis isomers, and the WEs were partially separated depending on the aliphatic-chain length. The WEs provided simple APCI spectra with [M+H](+) ions, the MS/MS spectra showed fragments, which allowed their identification. The method was applied for an analysis of the WE mixtures from jojoba oil and human hair and the results were compared with analogous data from an optimised RP-HPLC system. Copyright © 2013 Elsevier B.V. All rights reserved.

Semeia und Tekmeria im 5. Jahrhundert v. Chr.: Ein Beitrag zur Geschichte der ältesten griechischen Semiotik und Argumentationstechnik

Czech Academy of Sciences Publication Activity Database

Klouda, Jiří

2016-01-01

Roč. 139, 3/4 (2016), s. 275-299 ISSN 0024-4457 Institutional support: RVO:67985955 Keywords : theory of signs * theory of argumentation * the older Attic orators * Hippocratic Prognosticon * Dissoi logoi Subject RIV: AA - Philosophy ; Religion

Your Lung Operation: After Your Operation

Medline Plus

Full Text Available ... Membership Excelsior Surgical Society Officer Nominations ACS Clinical Congress Fitts Oration Contact MHSSPACS Society of Surgical Chairs ... Publications Resources Education Program Videos Contact Us Clinical Congress Clinical Congress 2018 Clinical Congress 2018 Postgraduate Courses ...

Ostomy Home Skills Program

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Full Text Available ... Membership Excelsior Surgical Society Officer Nominations ACS Clinical Congress Fitts Oration Contact MHSSPACS Society of Surgical Chairs ... Publications Resources Education Program Videos Contact Us Clinical Congress Clinical Congress 2018 Clinical Congress 2018 Postgraduate Courses ...

Esthetic Evaluation of Implant Crowns and Peri-Implant Soft Tissue in the Anterior Maxilla: Comparison and Reproducibility of Three Different Indices.

Science.gov (United States)

Tettamanti, Sandro; Millen, Christopher; Gavric, Jelena; Buser, Daniel; Belser, Urs C; Brägger, Urs; Wittneben, Julia-Gabriela

2016-06-01

A successful implant reconstruction with optimal esthetics consists of a visually pleasing prosthesis and complete and healthy surrounding soft tissue. In the current literature, numerous indices used to qualitatively assess esthetics have been described. However, studies comparing the indices and their reproducibility are scarce. The aim of this study was to compare three different esthetic indices for the evaluation of single implant-supported crowns. A total of 10 prosthodontists (P), 10 orthodontists (O), 10 general dentists (G), and 10 lay people (L) independently performed the same assessment using 30 photographs and corresponding casts with three different esthetic indices (Peri-Implant and Crown Index [PICI], Implant Crown Aesthetic Index [ICAI], "Pink Esthetic Score/White Esthetic Score [PES/WES]) and repeated the evaluations 4 weeks later. The PES/WES and the PICI showed significantly higher esthetic scores (pink, white, total) and clinical acceptance compared with the ICAI in all four groups and in both assessments. The highest intraobserver agreement was achieved using the PES/WES and the least with the ICAI. The mean Kappa per group ranged from 0.18 (group L with ICAI) to 0.63 (group G with PICI). In comparison with the ICAI, the PES/WES and PICI were more reproducible. Therefore, PES/WES and PICI seem to be more suitable as esthetic indices for single implant crowns. © 2015 Wiley Periodicals, Inc.

Promises, pitfalls and practicalities of prenatal whole exome sequencing.

Science.gov (United States)

Best, Sunayna; Wou, Karen; Vora, Neeta; Van der Veyver, Ignatia B; Wapner, Ronald; Chitty, Lyn S

2018-01-01

Prenatal genetic diagnosis provides information for pregnancy and perinatal decision-making and management. In several small series, prenatal whole exome sequencing (WES) approaches have identified genetic diagnoses when conventional tests (karyotype and microarray) were not diagnostic. Here, we review published prenatal WES studies and recent conference abstracts. Thirty-one studies were identified, with diagnostic rates in series of five or more fetuses varying between 6.2% and 80%. Differences in inclusion criteria and trio versus singleton approaches to sequencing largely account for the wide range of diagnostic rates. The data suggest that diagnostic yields will be greater in fetuses with multiple anomalies or in cases preselected following genetic review. Beyond its ability to improve diagnostic rates, we explore the potential of WES to improve understanding of prenatal presentations of genetic disorders and lethal fetal syndromes. We discuss prenatal phenotyping limitations, counselling challenges regarding variants of uncertain significance, incidental and secondary findings, and technical problems in WES. We review the practical, ethical, social and economic issues that must be considered before prenatal WES could become part of routine testing. Finally, we reflect upon the potential future of prenatal genetic diagnosis, including a move towards whole genome sequencing and non-invasive whole exome and whole genome testing. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

Genotyping of fanconi anemia patients by whole exome sequencing: advantages and challenges.

Directory of Open Access Journals (Sweden)

Kerstin Knies

Full Text Available Fanconi anemia (FA is a rare genomic instability syndrome. Disease-causing are biallelic mutations in any one of at least 15 genes encoding members of the FA/BRCA pathway of DNA-interstrand crosslink repair. Patients are diagnosed based upon phenotypical manifestations and the diagnosis of FA is confirmed by the hypersensitivity of cells to DNA interstrand crosslinking agents. Customary molecular diagnostics has become increasingly cumbersome, time-consuming and expensive the more FA genes have been identified. We performed Whole Exome Sequencing (WES in four FA patients in order to investigate the potential of this method for FA genotyping. In search of an optimal WES methodology we explored different enrichment and sequencing techniques. In each case we were able to identify the pathogenic mutations so that WES provided both, complementation group assignment and mutation detection in a single approach. The mutations included homozygous and heterozygous single base pair substitutions and a two-base-pair duplication in FANCJ, -D1, or -D2. Different WES strategies had no critical influence on the individual outcome. However, database errors and in particular pseudogenes impose obstacles that may prevent correct data perception and interpretation, and thus cause pitfalls. With these difficulties in mind, our results show that WES is a valuable tool for the molecular diagnosis of FA and a sufficiently safe technique, capable of engaging increasingly in competition with classical genetic approaches.

Evaluating the hydrological functioning and the supply of water provisioning services to support the ecosystem-water-food-energy nexus in the Arno river basin

Science.gov (United States)

Pacetti, Tommaso; Willaarts, Barbara; Caporali, Enrica; Schroeder Esselbach, Boris

2017-04-01

Water, flowing in a basin, underpins key provisioning ecosystem services like freshwater supply, food and energy production. River basin management largely determines the type of water-related ecosystem services (WES) that are provided and the extent to which trade-offs and synergies might arise. Gaining insights on the ecohydrological behavior of a basin and on the conflicting anthropic pressures on the available water resources allows to identify the most important WES, as well as the existence of WES supply and demand hotspots. This information is crucial for water resources management and, in the context of the European Union, also required to comply with the requirements of the Water Framework Directive (WFD). The purpose of this research is to quantify the provisioning WES in the upstream part of the Arno river basin (Central Italy) and identify WES hotspots and fluxes. Current information on how water is allocated in the Arno basin remains scarce, despite the increasing water demand by some sectors, particularly irrigation, and a number of emerging conflicts among users. It is expected that research outputs can support the improvement of the existing management framework, moving from the classical DPSIR (Driving forces, Pressure, State, Impact e Response) approach, where impacts must be reduced or mitigated, to a more proactive framework to support the sustainability of the Arno basin and meet the different policy goals. The eco-hydrological model SWAT (Soil Water Assessment Tool) is applied to spatially quantify the provision of WES. The preliminary results of this research indicate that the highest amount of water yield, i.e. net amount of water that contributes to streamflow and represents the main blue water fund, originates in the northern part of the basin, characterized by forest areas. In contrast, the southern part of the basin, which is mainly agriculturally used, gives a minor contribution to the overall water yield, in direct proportion to the

Ciceronas apie vertimą. Ką mums atskleidžia žodžių reikšmės | Cicero about Translation: Exploring the Meaning of Words

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Audronė Kučinskienė

2012-01-01

Full Text Available The author of the article reveals Cicero’s attitude towards translation, exploring some passages from his rhetorical and philosophical treatises which deal with translation from Greek to Latin, and paying most attention to the usage of words with the mean­ing “translate, translator”.To conclude, the regular Latin verb for “to trans­late” (convertere in Cicero’s usage implies neither the accuracy or literalism of translation. For a close literal translation he uses interpretari or such ex­pressions as ad verbum (verbum de verbo verbum e verbo, ad verbum exprimere, verbum pro verbo reddere. The verbs exprimere, explicare, reddere are used more or less metaphorically to express various aspects of translation from Greek, which includes also a free interpretation of the original and borrow­ing some elements from the original. According to our observations, Fin. I. 7 is the only case in Cicero’s extant scripts, as well as the first in Latin literature, when the verb transferre, while meaning “to trans­fer, to borrow, to use in context” comes closest to vertere. By contrast, the authors of I–II AD, such as Seneca, Pliny the Elder and the Younger, Quintilian use the word transferre with the meaning of transla­tion quite regularly.We argue that when Cicero calls himself not in­terpres, sed orator, he tries to indicate first of all not the closeness or freedom of translation, but rather the rhetorical power of his text. He is not afraid to use a word in not a very common sense, or two words for one in the original, or to create a new one if necessary, which may seem too bold for the interpretes indiserti not so skilled and well-trained in rhetorics. Cicero approached his work of translation without any pre­conceived rules, and the main standard referred to is his own taste based on the ruling principle of rhetor­ics – decorum, aptum, prepon – i.e. appropriateness. Cicero, as a translator as well as an orator, matches every

World Englishes, English as an International Language and Applied Linguistics

Science.gov (United States)

Kilickaya, Ferit

2009-01-01

The paper discusses World Englishes (WEs) in relation to English as an International Language (EIL) and Applied Linguistics. Taking into account Kachru's interesting but at the same time controversial debate about the status of English in its varieties, which are commonly called WEs and the opposing ideas presented by Quirk, it is aimed to present…

Antitussive arabinogalactan of Andrographis paniculata demonstrates synergistic effect with andrographolide.

Science.gov (United States)

Nosáľová, Gabriela; Majee, Sujay Kumar; Ghosh, Kanika; Raja, Washim; Chatterjee, Udipta Ranjan; Jureček, Ludovít; Ray, Bimalendu

2014-08-01

Traditional Indian medicines have been used in humans for thousands of years. While the link to a particular indication has been established in man, the active principle of the formulations often remains unknown. In this study, we aim to investigate the structural features and antitussive activity of fractions from Andrographis paniculata leaves. In vivo investigations of water extract (WE), and both ethanol-soluble (WES) and precipitated (WEP) fractions from WE on the citric-acid induced cough efforts and airways smooth muscle reactivity in guinea pigs were performed. Chemical, chromatographic and spectroscopic analysis revealed the existence of a highly branched pectic arabinogalactan (109kDa) in WEP and andrographolide in WES. WEP showed significant antitussive activity while the potencies of WE and WES are even higher. Neither WE nor WES significantly alter specific airway smooth muscle reactivity. Remarkably, the antitussive activity of arabinogalactan could be increased by synergistic action with andrographolide. Finally, traditional aqueous extraction method provides an arabinogalactan from A. paniculata, which stimulate biological response but without addiction. Copyright © 2014 Elsevier B.V. All rights reserved.

El discurso en la transición democrática: aplicaciones metodológicas para el análisis del discurso político.

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Antonio Pantoja Chaves.

2009-01-01

Full Text Available Resumen: El especial interés que contiene el proceso de Transición democrática en nuestro análisis reside en la aplicación de una serie de principios metodológicos que pueden ofrecernos conclusiones especialmente válidas para este período histórico. La finalidad del método consiste en determinar el antagonismo existente entre el orador y el auditorio a quien se dirige, y del mismo modo, analizar qué tipo de regulación está empleando en cada momento. La aplicación práctica del método sobre la serie de discursos seleccionados parte de la traducción de las manifestaciones del orador, sus expresiones, a siete regulaciones, con la intención de observar la tendencia de su discurso, la relación del orador con el auditorio. El orador, consciente del poder que posee su palabra, va a ir trazando su discurso, su pensamiento, el cual nos servirá de indicador esencial a la hora de iniciar un análisis coherente del mismo mediante el método de las regulaciones.Summary: The special interest that contains the process of democratic Transition in our analysis resides in the application of a series of methodological principles that can offer conclusions especially valid for this historical period. The purpose of the method consists of determining the existing opposition between the orator and the target auditorium, and in the same way, analyzing which type of regulation is using at all times. The practical application of the method on the series of chosen speeches departs from the translation of the declarations of the orator, his expressions, to seven regulations, with the intention of observing the tendency of his speech, the relation of the orator with the auditorium. The orator, conscious of the power that possesses his word, is going to be planning his speech, his thoughts, which will serve us as an essential indicator at the time of initiating a coherent analysis of it by means of the method of regulations.

Popular Public Discourse at Speakers' Corner: Negotiating Cultural Identities in Interaction

DEFF Research Database (Denmark)

McIlvenny, Paul

1996-01-01

, religious and general topical 'soap-box' oration. However, audiences are not passive receivers of rhetorical messages. They are active negotiators of interpretations and alignments that may conflict with the speaker's and other audience members' orientations to prior talk. Speakers' Corner is a space...

Between grammar and rhetoric : Dionysius of Halicarnassus on language, linguistics, and literature

NARCIS (Netherlands)

Jonge, Casper Constantijn de

2006-01-01

The Greek rhetorician and historian Dionysius of Halicarnassus was active in Rome at the end of the first century BC. In his rhetorical writings, he analyses the styles of classical Greek orators, historiographers and poets, including Homer, Lysias, Isocrates, Demosthenes and Thucydides. Dionysius

Losing Something In Translation: Turning Requirements Into Specifications

Science.gov (United States)

2016-06-01

specialized in Organizational Behavior. Perhaps the reader remembers the comedy routine in which a performer orates a lyrical, emotive passage in a deep...learned from the Technology Maturation and Risk Reduction phase and the Engineering and Manufacturing Development phase. These lessons learned, for

The Martial "Virtue" of Rhetoric in Machiavelli's "Art of War."

Science.gov (United States)

Wiethoff, William E.

1978-01-01

Argues that Machiavelli's inherent interest in pragmatic, "virtuous" applications of humanistic arts mandated both rhetorical form and matter in his composition of the "Art of War." Proposes that the work reveals Machiavelli's debt to the classically humane ideal of the warrior-orator. (JMF)

Erasmus of Rotterdam (1466-1536): renaissance advocate of the public role of medicine.

Science.gov (United States)

Albury, W R; Weisz, G M

2003-08-01

The great Renaissance scholar Erasmus of Rotterdam was a pioneering advocate of the importance of medicine for social as well as individual welfare. Erasmus' "Oration in praise of the art of medicine" (1518) illustrates his literary approach to this topic. Although the original version of his text did not address the state's role in promoting the health of the populace, Erasmus inserted new material on this topic into the "Oration" for a 1529 edition. This new material and references in some of his other writings from the same period indicate that it was in the 1520s that Erasmus first became a strong advocate of government intervention in public health matters. It is suggested that medical events in Erasmus' own life-his experiences both as a patient and as an observer of diseases-may explain why his interest in public health legislation increased significantly around this time.

Aquatic Plant Control Research Program. Proceedings, Annual Meeting, Aquatic Plant Control Research Program (23rd) Held in West Palm Beach, Florida on 14-17 November 1988

Science.gov (United States)

1989-06-01

85 CHEMICAL CONTROL TECHNOLOGY DEVELOPMENT .......... 91 Chemical Control Technology Development: Overview by Howard E. Westerdahl ...A, B, & C) Chemical Convod Technlo Development - H. Westerdah, WES, Presiding 8:00 a.m. Overview - Chemical Control Technology -H. Westerdahl , WES 8...Paul PO Box 631 1421 USPO & Custom House Vicksburg, MS 39181-0631 St. Paul, MN 55101-1479 Howard Westerdahl Tim Worley USAE Waterways Experiment Station

Thucydides’ Description of Democracy (2.37.1 and the EU-Convention of 2003

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Mogens Herman Hansen

2010-11-01

Full Text Available The view that the term demokratia was pejorative, and that Pericles praises liberty at the expense of democracy and so was misunderstood by the EU-convention, misreads the Funeral Oration and is contradicted by instances of Athenian praise of democracy.

Streptomyces roietensis sp. nov., an endophytic actinobacterium isolated from the surface-sterilized stem of jasmine rice, Oryza sativa KDML 105.

Science.gov (United States)

Kaewkla, Onuma; Franco, Christopher Milton Mathew

2017-11-01

An endophytic actinobacterium, strain WES2 T , was isolated from the stem of a jasmine rice plant collected from a paddy field in Thung Gura Rong Hai, Roi Et province, Thailand. As a result of a polyphasic study, this strain was identified as representing a novel member of the genus Streptomyces. This strain was a Gram-stain-positive, aerobic actinobacterium with well-developed substrate mycelia and forming chains of looped spores. The closest phylogenetic relations, which shared the highest 16S rRNA gene sequence similarity, were Streptomyces nogalater JCM 4799 T and Streptomyces lavenduligriseus NRRL-ISP 5487 T at 99.1 and 99.0 %, respectively. Chemotaxonomic data, including major fatty acids, cell wall components and major menaquinones, confirmed the affiliation of WES2 T to the genus Streptomyces. The data from the phylogenetic analysis, including physiological and biochemical studies and DNA-DNA hybridization, revealed the genotypic and phenotypic differentiation of WES2 T from the most closely related species with validly published names. The name proposed for the novel species is Streptomycesroietensis sp. nov. The type strain is WES2 T (=DSM 101729=NRRL B-65344).

Quantitative Profiling of Major Neutral Lipid Classes in Human Meibum by Direct Infusion Electrospray Ionization Mass Spectrometry

Science.gov (United States)

Chen, Jianzhong; Green, Kari B.; Nichols, Kelly K.

2013-01-01

Purpose. The purpose of this investigation was to better understand lipid composition in human meibum. Methods. Intact lipids in meibum samples were detected by direct infusion electrospray ionization mass spectrometry (ESI-MS) analysis in positive detection mode using sodium iodide (NaI) as an additive. The peak intensities of all major types of lipid species, that is, wax esters (WEs), cholesteryl esters (CEs), and diesters (DEs) were corrected for peak overlapping and isotopic distribution; an additional ionization efficiency correction was performed for WEs and CEs, which was simplified by the observation that the corresponding ionization efficiency was primarily dependent on the specific lipid class and saturation degree of the lipids while independent of the carbon chain length. A set of WE and CE standards was spiked in meibum samples for ionization efficiency determination and absolute quantitation. Results. The absolute amount (μmol/mg) for each of 51 WEs and 31 CEs in meibum samples was determined. The summed masses for 51 WEs and 31 CEs accounted for 48 ± 4% and 40 ± 2%, respectively, of the total meibum lipids. The mass percentages of saturated and unsaturated species were determined to be 75 ± 2% and 25 ± 1% for CEs and 14 ± 1% and 86 ± 1% for WEs. The profiles for two types of DEs were also obtained, which include 42 α,ω Type II DEs, and 21 ω Type I-St DEs. Conclusions. Major neutral lipid classes in meibum samples were quantitatively profiled by ESI-MS analysis with NaI additive. PMID:23847307

The Seventh Okoronkwo Kesandu Ogan Memorial Oration

African Journals Online (AJOL)

tackling illiteracy and discrimination against women. The intention is that ... health can work. 4 ... practices that limit women's exercise of their ... facilitate access to contraceptives against the ... expressed in adequate provision of resources.

Approach to the effect of phosphatic fertilizer and phosphogypsum upon the radioelement contents of some cultivated lands in the Egyptian nile delta

International Nuclear Information System (INIS)

Hussein, E.M.; Ahmed, H.A.H.

1997-01-01

The present work deals-for environmental importance with the estimation of radioelement contents 238 U, 226 Ra, 232 Th and 40 K in non fertilized soil, fertilized soil (crops), fertilized soil (vegetables) and samples from the bottoms of the local drainage systems collected from four sites (Govern orates) of egyptian delta. This work therefore aims at assessing eventual concentration and build up of the natural-radioactivity in the Egyptian soil treated by the locally produced single superphosphate fertilizer and phosphogypsum. A total number (42) of samples were collected from the following sites (Govern orates); 1) El-Qalyobia (Shebin El-Qanater and Abu-Zaabal); 2) El-Sharqia (Inshas and Minia El-kamh); 3) El-Dakahlia (El-Mansoura); and 4) El-Menoufia (Tala). From each locality two samples of non-fertilized soil, two samples of non-fertilized soil, two samples of fertilized soil (crops), two samples of fertilized soil (vegetables), and sample the drainage system were obtained.

’n Retoriese analise van die vyf lykdigte in T.T. Cloete se Allotroop

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L. Viljoen

1995-05-01

This article works from the premise that these poems form part o f a tradition that can he traced back to the funerary poetry of the Dutch Renaissance and from there to the funeral orations of Classical times. After referring to the current revival of interest in rhetoric, attention is given to the role which rhetoric played in Renaissance poetics and the influence it had on the practice of writing funerary poetry. The funerary poems in Cloete's Allotroop are then analysed, making use of the Renaissance descriptions of and prescriptions for funerary poetry researched by S.F. Witstein in Funeraire poëzie in de Nederlandse Renaissance. These analyses prove that Cloete’s poems make use of the elements basic to the Renaissance funerary poem and the classical funeral oration namely praise (laus, mourning (luctus and consolation (consolatio and that the rhetorical terminology devised centuries ago can still be useful in the reading of these poems.

La retórica aristotélica y la oratoria de su tiempo (sobre el ejemplo de Lisias III

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Francisco Cortés Gabaudan

1998-12-01

Full Text Available Aristotle's Rhetoric is a descriptive text to a greater extent than normally recognised and so our understanding of Aristotle can be improved with the analysis of speeches previous to him; as a case study, the third speech of Lysias has been chosen. The argumentation of judicial speeches previous to Aristotle was built with enthymemes whose first premises are based on emotions and characters explaining human behaviour; therefore the first purpose of Rhetoric 11.2-11 (about emotions and 11.2-17 (about characters was to supply the orators with first premises. In those speeches the emotions of the audience were stirred up by enthymemes; therefore Aristotle accepted that the orator could use emotions in this rational and logic way. Nevertheless he condemned the arousing of emotions by direct and irrational requests, a procedure found in the judicial speeches. This way the apparent contradictory treatment of emotions in Aristotle's Rhetoric can be solved.

Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.

Science.gov (United States)

Tammimies, Kristiina; Marshall, Christian R; Walker, Susan; Kaur, Gaganjot; Thiruvahindrapuram, Bhooma; Lionel, Anath C; Yuen, Ryan K C; Uddin, Mohammed; Roberts, Wendy; Weksberg, Rosanna; Woodbury-Smith, Marc; Zwaigenbaum, Lonnie; Anagnostou, Evdokia; Wang, Zhuozhi; Wei, John; Howe, Jennifer L; Gazzellone, Matthew J; Lau, Lynette; Sung, Wilson W L; Whitten, Kathy; Vardy, Cathy; Crosbie, Victoria; Tsang, Brian; D'Abate, Lia; Tong, Winnie W L; Luscombe, Sandra; Doyle, Tyna; Carter, Melissa T; Szatmari, Peter; Stuckless, Susan; Merico, Daniele; Stavropoulos, Dimitri J; Scherer, Stephen W; Fernandez, Bridget A

2015-09-01

The use of genome-wide tests to provide molecular diagnosis for individuals with autism spectrum disorder (ASD) requires more study. To perform chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in a heterogeneous group of children with ASD to determine the molecular diagnostic yield of these tests in a sample typical of a developmental pediatric clinic. The sample consisted of 258 consecutively ascertained unrelated children with ASD who underwent detailed assessments to define morphology scores based on the presence of major congenital abnormalities and minor physical anomalies. The children were recruited between 2008 and 2013 in Newfoundland and Labrador, Canada. The probands were stratified into 3 groups of increasing morphological severity: essential, equivocal, and complex (scores of 0-3, 4-5, and ≥6). All probands underwent CMA, with WES performed for 95 proband-parent trios. The overall molecular diagnostic yield for CMA and WES in a population-based ASD sample stratified in 3 phenotypic groups. Of 258 probands, 24 (9.3%, 95%CI, 6.1%-13.5%) received a molecular diagnosis from CMA and 8 of 95 (8.4%, 95%CI, 3.7%-15.9%) from WES. The yields were statistically different between the morphological groups. Among the children who underwent both CMA and WES testing, the estimated proportion with an identifiable genetic etiology was 15.8% (95%CI, 9.1%-24.7%; 15/95 children). This included 2 children who received molecular diagnoses from both tests. The combined yield was significantly higher in the complex group when compared with the essential group (pairwise comparison, P = .002). [table: see text]. Among a heterogeneous sample of children with ASD, the molecular diagnostic yields of CMA and WES were comparable, and the combined molecular diagnostic yield was higher in children with more complex morphological phenotypes in comparison with the children in the essential category. If replicated in additional populations, these findings may

Heckling in Hyde Park: Verbal Audience Participation in Popular Public Discourse

DEFF Research Database (Denmark)

McIlvenny, Paul

1996-01-01

Speakers' Corner is a multicultural setting in a London park at which the general public can actively participate in popular debate. A successful 'soap-box' orator should attract and keep an audience, elicit support from the crowd and gain applause; indeed, a mastery of the crowd, the discourse...

WES: A well test analysis expert system

International Nuclear Information System (INIS)

Mensch, A.

1988-06-01

This report describes part of the development of an expert system in the domain of well-test analysis. This work has been done during my final internship, completed at the Lawrence Berkeley Laboratory. The report is divided in three parts: the first one gives a description of the state of the project at the time I first began to work on it, and raises some problems that have to be solved. The second section shows the results that have been reached, and the last one draws conclusions from these results and proposes extensions that would be useful in the future

Evaluation of Upland Disposal of Oakland Harbor, California, Sediment; Volume I: Turning Basin Sediments

Science.gov (United States)

1992-10-01

infiltration studies ( Westerdahl and Skogerboe 1982). Extensive field 53 verification studies have been conducted with the WES Rainfall Simulator...Lysimeter System on a wide range of Corps project sites ( Westerdahl and Skogerboe 1982, Lee and Skogerboe 1984, Skogerboe et al. 1987). The WES Rain- fall...Vicksburg, MS. Winer, B. J. 1971. Statistical Principles in Experimental Design, McGraw- Hill Book Company, New York. Westerdahl , H. E., and Skogerboe, J

New Bedford Harbor Superfund Project, Acushnet River Estuary Engineering Feasibility Study of Dredging and Dredged Material Disposal Alternatives. Report 4. Surface Runoff Quality Evaluation for Confined Disposal

Science.gov (United States)

1988-01-01

infiltration studies ( Westerdahl and Skogerboe 1982). Exten- sive field verification studies have been conducted with the WES Rainfall Simulator...Lysimeter System on a wide range of USACE project sites ( Westerdahl and Skogerboe 1982, Lee and Skogerboe 1984, Skogerboe et al. 1987). The WES Rainfall...Criteria for Water 1986,"’ Criteria and Standards Division, Washington, DC. Westerdahl , H. E., and Skogerboe, J. G. 1982. "Realistic Rainfall and Water

Whole-exome sequencing gives additional benefits compared to candidate gene sequencing in the molecular diagnosis of children with growth hormone or IGF-1 insensitivity.

Science.gov (United States)

Shapiro, Lucy; Chatterjee, Sumana; Ramadan, Dina G; Davies, Kate M; Savage, Martin O; Metherell, Louise A; Storr, Helen L

2017-12-01

GH insensitivity (GHI) is characterised by short stature, IGF-1 deficiency and normal/elevated serum GH. IGF-1 insensitivity results in pre- and post-natal growth failure with normal/high IGF-1 levels. The prevalence of genetic defects is unknown. To identify the underlying genetic diagnoses in a paediatric cohort with GH or IGF-1 insensitivity using candidate gene (CGS) and whole-exome sequencing (WES) and assess factors associated with the discovery of a genetic defect. We undertook a prospective study of 132 patients with short stature and suspected GH or IGF-1 insensitivity referred to our centre for genetic analysis. 107 (96 GHI, 88 probands; 11 IGF-1 insensitivity, 9 probands) underwent CGS. WES was performed in those with no defined genetic aetiology following CGS. A genetic diagnosis was discovered 38/107 (36%) patients (32% probands) by CGS. WES revealed 11 patients with genetic variants in genes known to cause short stature. A further 2 patients had hypomethylation in the H19/IGF2 region or mUPD7 consistent with Silver-Russell Syndrome (total with genetic diagnosis 51/107, 48% or 41/97, 42% probands). WES also identified homozygous putative variants in FANCA and PHKB in 2 patients. Low height SDS and consanguinity were highly predictive for identifying a genetic defect. Comprehensive genetic testing confirms the genetic heterogeneity of GH/IGF-1 insensitivity and successfully identified the genetic aetiology in a significant proportion of cases. WES is rapid and may isolate genetic variants that have been missed by traditional clinically driven genetic testing. This emphasises the benefits of specialist diagnostic centres. © 2017 European Society of Endocrinology.

Identification of innate immunodeficiencies by whole genome sequencing

DEFF Research Database (Denmark)

Mogensen, Trine; Christiansen, Mette; Veirum, Jens Erik

2014-01-01

encephalitis or other herpes simplex virus (HSV) disease manifestations. The goal is to identify host factors in innate immunity which may explain the hitherto unknown mechanism underlying differential susceptibility to HSV infections between individuals. Such knowledge may have clinical and therapeutical...... implications. Methods: As part of a pilot study we performed WES on 4 patients with herpes encephalitis or mucocutaneous manifestations of HSV infection. WES was performed with Illumina technology (Illumina HiSeq/MiSeq) and analyzed PolyPhen-2 (Polymorphism Phenotyping v2) PhyloP, and SIFT prediction software......, TBK1 and Unc93B) may contribute to the development of herpes encephalitis. Common to these genetic defects is that they lead to reduced antiviral interferon (IFN) responses. In this study whole exome sequencing (WES) was performed to identify mutations associated with susceptibility to herpes...

Liberal Education: A Literary Black Hole?

Science.gov (United States)

Pederson, Tom

1989-01-01

An overview of the historical traditions presented by Bruce Kimball in his "Orators and Philosophers: A History of the Idea of Liberal Education" is presented. The significance of the structure of the Catholic and other Christian churches in perpetuating the ideal and reality of a liberal arts education is discussed. (Author/MLW)

Interagency Research Conference (15th) Held in Vicksburg, Mississippi on 3-5 November 1987

Science.gov (United States)

1987-11-05

Stepped Spillway USBR H-7b Labyrinth Spillways USBR H-7d Scour Downstream from Stilling Basins WES H-Ba Analyses of Hydroturbine Vibrations TVA H-Be... Hydroturbine Flow Measurement Using the Pressure- Time Method TVA The following technology transfer methods were given by the participants: a. Technical...7c Stilling Basin Damage Due to Erosion USBR H-7d Scour Downstream from Stilling Basins WES H-8a Analyses of Hydroturbine Vibrations TVA H-8b

Borehole Plugging-Materials Development Program

International Nuclear Information System (INIS)

Gulick, C.W. Jr.

1978-06-01

This report discusses the background and first year's results of the grouting materials development program for plugging boreholes associated with the Nuclear Waste Isolation Pilot Plant. The grouts are to be pumpable, impermeable, and durable for many thousands of years. The work was done at the Concrete Laboratory of the U.S. Army Engineer Waterways Experiment Station (WES), Vicksburg, Mississippi. The workability, strength, porosity, bonding, expansion, and permeability data are summarized and discussed. The work is continuing at WES

Whole-exome sequencing links TMCO1 defect syndrome with cerebro-facio-thoracic dysplasia.

Science.gov (United States)

Pehlivan, Davut; Karaca, Ender; Aydin, Hatip; Beck, Christine R; Gambin, Tomasz; Muzny, Donna M; Bilge Geckinli, B; Karaman, Ali; Jhangiani, Shalini N; Gibbs, Richard A; Lupski, James R

2014-09-01

Whole-exome sequencing (WES) is a type of disruptive technology that has tremendous influence on human and clinical genetics research. An efficient and cost-effective method, WES is now widely used as a diagnostic tool for identifying the molecular basis of genetic syndromes that are often challenging to diagnose. Here we report a patient with a clinical diagnosis of cerebro-facio-thoracic dysplasia (CFTD; MIM#213980) in whom we identified a homozygous splice-site mutation in the transmembrane and coiled-coil domains 1 (TMCO1) gene using WES. TMCO1 mutations cause craniofacial dysmorphism, skeletal anomalies characterized by multiple malformations of the vertebrae and ribs, and intellectual disability (MIM#614132). A retrospective review revealed that clinical manifestations of both syndromes are very similar and overlap remarkably. We propose that mutations of TMCO1 are not only responsible for craniofacial dysmorphism, skeletal anomalies and mental retardation syndrome but also for CFTD.

The Legitimization of Dialectic: Socratic Strategy in the "Gorgias."

Science.gov (United States)

Palmerton, Patricia

In the "Gorgias," Plato focuses attention upon the value of dialectic as opposed to rhetoric, as well as the status of orators as opposed to philosophers. Through his agent, Socrates, Plato confirms dialectic as a legitimate endeavor while calling into question the place of rhetoric. Socrates is portrayed as a director who enacts a…

Author Details

African Journals Online (AJOL)

Alumona, Victor S. Vol 18, No 1 (2004) - Articles Gorgias' scepticism regarding Greek social class distinctions in the Funeral Oration (DK.82.BSa) Abstract PDF. ISSN: 1016-0728. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners ...

Ramus Revisited: The Uses and Limits of Classical Rhetoric.

Science.gov (United States)

Walpole, Jane R.

Everything taught as rhetoric today can be traced to Aristotle, but his rhetoric needs to be updated. The five elements of his rhetoric--invention, arrangement, style, memory, and delivery--were designed for public orators, but rhetoric has since come to mean the written rather than the spoken word. Peter Ramus redefined rhetoric in the sixteenth…

Clinical Applicability of Whole-Exome Sequencing Exemplified by a Study in Young Adults with the Advanced Cryptogenic Cholestatic Liver Diseases

Directory of Open Access Journals (Sweden)

Maria Kulecka

2017-01-01

Full Text Available Background. The proper use of new medical tests in clinical practice requires the establishment of their value and range of diagnostic usefulness. While whole-exome sequencing (WES has already entered the medical practice, recognizing its diagnostic usefulness in multifactorial diseases has not yet been achieved. Aims. The objective of this study was to establish usability of WES in determining genetic background of chronic cholestatic liver disease (CLD in young patients. Methods. WES was performed on six young patients (between 17 and 22 years old with advanced fibrosis or cirrhosis due to CLD and their immediate families. Sequencing was performed on an Ion Proton sequencer. Results. On average, 19,673 variants were identified, of which from 7 to 14 variants of an individual were nonsynonymous, homozygous, recessively inherited, and considered in silico as pathogenic. Although monogenic cause of CLD has not been determined, several heterozygous rare variants and polymorphisms were uncovered in genes previously known to be associated with CLD, including ATP8B1, ABCB11, RXRA, and ABCC4, indicative of multifactorial genetic background. Conclusions. WES is a potentially useful diagnostic tool in determining genetic background of multifactorial diseases, but its main limitation results from the lack of opportunities for direct linkage between the uncovered genetic variants and molecular mechanisms of disease.

Exome sequencing unravels unexpected differential diagnoses in individuals with the tentative diagnosis of Coffin-Siris and Nicolaides-Baraitser syndromes.

Science.gov (United States)

Bramswig, Nuria C; Lüdecke, Hermann-Josef; Alanay, Yasemin; Albrecht, Beate; Barthelmie, Alexander; Boduroglu, Koray; Braunholz, Diana; Caliebe, Almuth; Chrzanowska, Krystyna H; Czeschik, Johanna Christina; Endele, Sabine; Graf, Elisabeth; Guillén-Navarro, Encarna; Kiper, Pelin Özlem Simsek; López-González, Vanesa; Parenti, Ilaria; Pozojevic, Jelena; Utine, Gulen Eda; Wieland, Thomas; Kaiser, Frank J; Wollnik, Bernd; Strom, Tim M; Wieczorek, Dagmar

2015-06-01

Coffin-Siris syndrome (CSS) and Nicolaides-Baraitser syndrome (NCBRS) are rare intellectual disability/congenital malformation syndromes that represent distinct entities but show considerable clinical overlap. They are caused by mutations in genes encoding members of the BRG1- and BRM-associated factor (BAF) complex. However, there are a number of patients with the clinical diagnosis of CSS or NCBRS in whom the causative mutation has not been identified. In this study, we performed trio-based whole-exome sequencing (WES) in ten previously described but unsolved individuals with the tentative diagnosis of CSS or NCBRS and found causative mutations in nine out of ten individuals. Interestingly, our WES analysis disclosed overlapping differential diagnoses including Wiedemann-Steiner, Kabuki, and Adams-Oliver syndromes. In addition, most likely causative de novo mutations were identified in GRIN2A and SHANK3. Moreover, trio-based WES detected SMARCA2 and SMARCA4 deletions, which had not been annotated in a previous Haloplex target enrichment and next-generation sequencing of known CSS/NCBRS genes emphasizing the advantages of WES as a diagnostic tool. In summary, we discuss the phenotypic and diagnostic challenges in clinical genetics, establish important differential diagnoses, and emphasize the cardinal features and the broad clinical spectrum of BAF complex disorders and other disorders caused by mutations in epigenetic landscapers.

Molecular diagnostic experience of whole-exome sequencing in adult patients.

Science.gov (United States)

Posey, Jennifer E; Rosenfeld, Jill A; James, Regis A; Bainbridge, Matthew; Niu, Zhiyv; Wang, Xia; Dhar, Shweta; Wiszniewski, Wojciech; Akdemir, Zeynep H C; Gambin, Tomasz; Xia, Fan; Person, Richard E; Walkiewicz, Magdalena; Shaw, Chad A; Sutton, V Reid; Beaudet, Arthur L; Muzny, Donna; Eng, Christine M; Yang, Yaping; Gibbs, Richard A; Lupski, James R; Boerwinkle, Eric; Plon, Sharon E

2016-07-01

Whole-exome sequencing (WES) is increasingly used as a diagnostic tool in medicine, but prior reports focus on predominantly pediatric cohorts with neurologic or developmental disorders. We describe the diagnostic yield and characteristics of WES in adults. We performed a retrospective analysis of consecutive WES reports for adults from a diagnostic laboratory. Phenotype composition was determined using Human Phenotype Ontology terms. Molecular diagnoses were reported for 17.5% (85/486) of adults, which is lower than that for a primarily pediatric population (25.2%; P = 0.0003); the diagnostic rate was higher (23.9%) for those 18-30 years of age compared to patients older than 30 years (10.4%; P = 0.0001). Dual Mendelian diagnoses contributed to 7% of diagnoses, revealing blended phenotypes. Diagnoses were more frequent among individuals with abnormalities of the nervous system, skeletal system, head/neck, and growth. Diagnostic rate was independent of family history information, and de novo mutations contributed to 61.4% of autosomal dominant diagnoses. Early WES experience in adults demonstrates molecular diagnoses in a substantial proportion of patients, informing clinical management, recurrence risk, and recommendations for relatives. A positive family history was not predictive, consistent with molecular diagnoses often revealed by de novo events, informing the Mendelian basis of genetic disease in adults.Genet Med 18 7, 678-685.

Whole-exome sequencing analysis of Waardenburg syndrome in a Chinese family

Science.gov (United States)

Chen, Dezhong; Zhao, Na; Wang, Jing; Li, Zhuoyu; Wu, Changxin; Fu, Jie; Xiao, Han

2017-01-01

Waardenburg syndrome (WS) is a dominantly inherited, genetically heterogeneous auditory-pigmentary syndrome characterized by non-progressive sensorineural hearing loss and iris discoloration. By whole-exome sequencing (WES), we identified a nonsense mutation (c.598C>T) in PAX3 gene, predicted to be disease causing by in silico analysis. This is the first report of genetically diagnosed case of WS PAX3 c.598C>T nonsense mutation in Chinese ethnic origin by WES and in silico functional prediction methods. PMID:28690861

Whole-exome sequencing analysis of Waardenburg syndrome in a Chinese family.

Science.gov (United States)

Chen, Dezhong; Zhao, Na; Wang, Jing; Li, Zhuoyu; Wu, Changxin; Fu, Jie; Xiao, Han

2017-01-01

Waardenburg syndrome (WS) is a dominantly inherited, genetically heterogeneous auditory-pigmentary syndrome characterized by non-progressive sensorineural hearing loss and iris discoloration. By whole-exome sequencing (WES), we identified a nonsense mutation (c.598C>T) in PAX3 gene, predicted to be disease causing by in silico analysis. This is the first report of genetically diagnosed case of WS PAX3 c.598C>T nonsense mutation in Chinese ethnic origin by WES and in silico functional prediction methods.

Recommendations to the NRC for soil cover systems over uranium mill tailings and low-level radioactive wastes

International Nuclear Information System (INIS)

Bennett, R.D.; Kimbrell, A.F.

1991-02-01

The US Army Engineer Waterways Experiment Station (WES) has provided recommendations to the US Nuclear Regulatory Commission (NRC) for the selection placement, compaction, testing, and acceptance of soils proposed to be placed in cover systems over uranium mill tailings and low-level radioactive wastes. The recommendations from WES are contained in three volumes of NUREG/CR-5432. Volume 1 identifies the various soil types and engineering properties that are needed to fulfill important soil cover functions. The identified soils are then ranked according to their capability to perform the low-permeability and filter and drainage functions. Volume 2 provides recommendations for conducting pertinent laboratory and field tests to ensure acceptable soil cover performance. Volume 3 covers recommendations from WES on proper field construction methods including guidance on quality control testing and inspections. Recommendations are given for sealing penetrations (e.g., observation wells) that are required to penetrate covers for environmental monitoring of disposal facility performance. 30 refs., 6 figs., 9 tabs

Electrochemical Characterization of O2 Plasma Functionalized Multi-Walled Carbon Nanotube Electrode for Legionella pneumophila DNA Sensor

Science.gov (United States)

Park, Eun Jin; Lee, Jun-Yong; Hyup Kim, Jun; Kug Kim, Sun; Lee, Cheol Jin; Min, Nam Ki

2010-08-01

An electrochemical DNA sensor for Legionella pneumophila detection was constructed using O2 plasma functionalized multi-walled carbon nanotube (MWCNT) film as a working electrode (WE). The cyclic voltammetry (CV) results revealed that the electrocatalytic activity of plasma functionalized MWCNT (pf-MWCNT) significantly changed depending on O2 plasma treatment time due to some oxygen containing functional groups on the pf-MWCNT surface. Scanning electron microscope (SEM) images and X-ray photoelectron spectroscopy (XPS) spectra were also presented the changes of their surface morphologies and oxygen composition before and after plasma treatment. From a comparison study, it was found that the pf-MWCNT WEs had higher electrocatalytic activity and more capability of probe DNA immobilization: therefore, electrochemical signal changes by probe DNA immobilization and hybridization on pf-MWCNT WEs were larger than on Au WEs. The pf-MWCNT based DNA sensor was able to detect a concentration range of 10 pM-100 nM of target DNA to detect L. pneumophila.

Epicuticular Wax in Developing Olives (Olea europaea) Is Highly Dependent upon Cultivar and Fruit Ripeness.

Science.gov (United States)

Vichi, Stefania; Cortés-Francisco, Nuria; Caixach, Josep; Barrios, Gonçal; Mateu, Jordi; Ninot, Antonia; Romero, Agustí

2016-08-03

The epicuticular wax (EW) layer is located on the surface of most plant organs. It provides the cuticle with most of its properties and is the primary barrier against biotic and abiotic stress. Despite the importance of Olea europaea cultivation, few studies have characterized the EW covering leaves and olives, which could be involved in resistance to both infection and environmental conditions. In the present study, wide-ranging screening was carried out using direct-injection electrospray ionization coupled to high-resolution mass spectrometry to analyze EW in developing olives of nine varieties. The proportions of EW fractions [wax esters (WEs), diacylglycerols, triacylglycerols (TAGs), triterpenic acids, and aldehydes] strongly depended upon the olive cultivar and, in only a few cases, were influenced by the sampling date. The specific compositions of the major fractions, WEs and TAGs, were strictly related to the cultivar, while the degree of unsaturation and chain length of the WEs evolved throughout the 4 weeks prior to the olive turning color.

Die Ontstaan en Ontwikkeling van die Pan-Afrikanisme en due implikasies daarvan

Directory of Open Access Journals (Sweden)

A. J.H. van der Walt

1961-03-01

Full Text Available Dit was nie voor 1880 dat tropiese Afrika, dil is die grootste gedeelte van Wes-, Oos- en Midde-Afrika, deur ontdekkingsreisigers,handelaars en sendelinge tot so ’11 mate ontsluit is, dat dit in die vaarwater van die wêreldpolitiek geraak het nie. Lank voor hierdie tyd is natuurlik steunpunte aan die Wes-, Suid- en Ooskusdeur die Portugese en later die Nederlanders en Engelse eset ter wille van óf dieslawehandel en/óf as steunpunte op dielarig handelsweg na die ryke Ooste.

Ontwikkelingsekonomie — Bestek en metode vir die studie daarvan

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H.J. Weber

1974-03-01

Full Text Available Kennis van die probleme van onderontwikkelde gebiede is baie oud. Sodra verskille in ontwikkeldheid, hetsy op militêre, ekonomiese of ander gebiede duidelik word, en as sodanig erken word, wys die probleme van die minderontwikkelde gebiede hulself uit. Die ekonomiese geskiedenis is vol sodanige erkende verskille o.a. Hellenistiese kultuursentra, Imperiale Rome, Byzantium en sy florerende stadstaat; Noord- en Wes- Europa na die ontdekking van die nuwe wêreld en die vasstelling van effektiewe marinekommunikasie tussen Wes- Europa, Amerika en Oos-Asië.

De novo FBXO11 mutations are associated with intellectual disability and behavioural anomalies.

Science.gov (United States)

Fritzen, Daniel; Kuechler, Alma; Grimmel, Mona; Becker, Jessica; Peters, Sophia; Sturm, Marc; Hundertmark, Hela; Schmidt, Axel; Kreiß, Martina; Strom, Tim M; Wieczorek, Dagmar; Haack, Tobias B; Beck-Wödl, Stefanie; Cremer, Kirsten; Engels, Hartmut

2018-05-01

Intellectual disability (ID) has an estimated prevalence of 1.5-2%. In most affected individuals, its genetic basis remains unclear. Whole exome sequencing (WES) studies have identified a multitude of novel causative gene defects and have shown that a large proportion of sporadic ID cases results from de novo mutations. Here, we present two unrelated individuals with similar clinical features and deleterious de novo variants in FBXO11 detected by WES. Individual 1, a 14-year-old boy, has mild ID as well as mild microcephaly, corrected cleft lip and alveolus, hyperkinetic disorder, mild brain atrophy and minor facial dysmorphism. WES detected a heterozygous de novo 1 bp insertion in the splice donor site of exon 3. Individual 2, a 3-year-old boy, showed ID and pre- and postnatal growth retardation, postnatal mild microcephaly, hyperkinetic and restless behaviour, as well as mild dysmorphism. WES detected a heterozygous de novo frameshift mutation. While ten individuals with ID and de novo variants in FBXO11 have been reported as part of larger studies, only one of the reports has some additional clinical data. Interestingly, the latter individual carries the identical mutation as our individual 2 and also displays ID, intrauterine growth retardation, microcephaly, behavioural anomalies, and dysmorphisms. Thus, we confirm deleterious de novo mutations in FBXO11 as a cause of ID and start the delineation of the associated clinical picture which may also comprise postnatal microcephaly or borderline small head size and behavioural anomalies.

Whole-exome sequencing and an iPSC-derived cardiomyocyte model provides a powerful platform for gene discovery in left ventricular hypertrophy

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Degui eZhi

2012-05-01

Full Text Available Rationale: Left ventricular hypertrophy (LVH is a heritable predictor of cardiovascular disease, particularly in blacks. Objective: Determine the feasibility of combining evidence from two distinct but complimentary experimental approaches to identify novel genetic predictors of increased LV mass . Methods: Whole exome sequencing (WES was conducted in 7 African American sibling trios ascertained on high average familial LV mass indexed to height (LVMHT. WES identified 31,426 missense or nonsense mutations (MS/NS which were examined for association with LVMHT using linear mixed models adjusted for age, sex, body weight, and family relationship. To functionally assess WES findings, human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM were stimulated to induce hypertrophy; mRNA sequencing was used to determine expression differences associated with hypertrophy onset. Results: After correction for multiple testing, 295 MS/NS variants in 265 genes were associated with LVMHT. We identified 44 of 265 WES genes differentially expressed (P<0.05 in hypertrophied cells. To further prioritize these 44 candidates, 7 supportive statistical and annotation-based criteria were used to evaluate the relevance of these genes. Five genes, HLA-B, HTT, MTSS1, SLC5A12, THBS1, were each supported by 3 criteria. THBS1 encodes an adhesive glycoprotein that promotes matrix preservation in pressure-overload LVH and harbors conserved and predicted damaging variants. Conclusions: Combining evidence from cutting-edge genetic and cellular experiments can enable identification of novel LVH risk loci.

Fission characteristics of Ra formed in heavy-ion induced reactions

Indian Academy of Sciences (India)

A Kramers-modified statistical model is used to calculate the cross-section of the evap- oration residue, fission ... where ρCN and ρsad are the level density of the compound nucleus at the ground and saddle points ... where P(K) is the probability that the system is in a given K. P(K) = T ..... time to be emitted before fission.

Alkaline water electrolysis technology for Space Station regenerative fuel cell energy storage

Science.gov (United States)

Schubert, F. H.; Hoberecht, M. A.; Le, M.

1986-01-01

The regenerative fuel cell system (RFCS), designed for application to the Space Station energy storage system, is based on state-of-the-art alkaline electrolyte technology and incorporates a dedicated fuel cell system (FCS) and water electrolysis subsystem (WES). In the present study, emphasis is placed on the WES portion of the RFCS. To ensure RFCS availability for the Space Station, the RFCS Space Station Prototype design was undertaken which included a 46-cell 0.93 cu m static feed water electrolysis module and three integrated mechanical components.

Incorporating big data into treatment plan evaluation: Development of statistical DVH metrics and visualization dashboards.

Science.gov (United States)

Mayo, Charles S; Yao, John; Eisbruch, Avraham; Balter, James M; Litzenberg, Dale W; Matuszak, Martha M; Kessler, Marc L; Weyburn, Grant; Anderson, Carlos J; Owen, Dawn; Jackson, William C; Haken, Randall Ten

2017-01-01

To develop statistical dose-volume histogram (DVH)-based metrics and a visualization method to quantify the comparison of treatment plans with historical experience and among different institutions. The descriptive statistical summary (ie, median, first and third quartiles, and 95% confidence intervals) of volume-normalized DVH curve sets of past experiences was visualized through the creation of statistical DVH plots. Detailed distribution parameters were calculated and stored in JavaScript Object Notation files to facilitate management, including transfer and potential multi-institutional comparisons. In the treatment plan evaluation, structure DVH curves were scored against computed statistical DVHs and weighted experience scores (WESs). Individual, clinically used, DVH-based metrics were integrated into a generalized evaluation metric (GEM) as a priority-weighted sum of normalized incomplete gamma functions. Historical treatment plans for 351 patients with head and neck cancer, 104 with prostate cancer who were treated with conventional fractionation, and 94 with liver cancer who were treated with stereotactic body radiation therapy were analyzed to demonstrate the usage of statistical DVH, WES, and GEM in a plan evaluation. A shareable dashboard plugin was created to display statistical DVHs and integrate GEM and WES scores into a clinical plan evaluation within the treatment planning system. Benchmarking with normal tissue complication probability scores was carried out to compare the behavior of GEM and WES scores. DVH curves from historical treatment plans were characterized and presented, with difficult-to-spare structures (ie, frequently compromised organs at risk) identified. Quantitative evaluations by GEM and/or WES compared favorably with the normal tissue complication probability Lyman-Kutcher-Burman model, transforming a set of discrete threshold-priority limits into a continuous model reflecting physician objectives and historical experience

The plant economics spectrum is structured by leaf habits and growth forms across subtropical species.

Science.gov (United States)

Zhao, Yan-Tao; Ali, Arshad; Yan, En-Rong

2017-02-01

The plant economics spectrum that integrates the combination of leaf and wood syndromes provides a useful framework for the examination of species strategies at the whole-plant level. However, it remains unclear how species that differ in leaf habits and growth forms are integrated within the plant economics spectrum in subtropical forests. We measured five leaf and six wood traits across 58 subtropical plant species, which represented two leaf habits (evergreen vs deciduous) and two growth forms (tree vs shrub) in eastern China. Principal component analysis (PCA) was employed separately to construct the leaf (LES), wood (WES) and whole-plant (WPES) economics spectra. Leaf and wood traits are highly intra- and intercorrelated, thus defining not only the LES and WES, but also a WPES. Multi-trait variations in PCAs revealed that the traits which were representative of the acquisitive strategy, i.e., cheap tissue investment and rapid returns on that investment, were clustered at one end, while traits that represented the conservative strategy, i.e., expensive tissue investment and slower returns, were clustered at other end in each of the axes of the leaf and wood syndromes (PC1-axis) and the plant height strategy (PC2-axis). The local WPES, LES and WES were tightly correlated with each other. Evergreens shaped the conservative side, while deciduous species structured the acquisitive side of the WPES and LES. With respect to plant height strategies, trees formulated the acquisitive side and shrub species made up the conservative side of the WPES, LES and WES. In conclusion, our results suggested that the LES and WES were coordinated to a WPES for subtropical species. The finding of this local spectrum of plant form and function would be beneficial for modeling nutrient fluxes and species compositions in the changing climate, but also for understanding species strategies in an evolutionary context. © The Author 2016. Published by Oxford University Press. All rights

Listening for Noise in Political Thought

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Bruce Buchan

2012-11-01

Full Text Available The acoustic dimension of political philosophy has rarely attracted serious attention, in part because scholars have tended to assume that political theories, ideas, and concepts, exist as abstract entities that are often noiselessly communicated in written texts. And yet, the noisy communication of political ideas whether in the form of Socratic dialogues, Churchillian orations, or in the hushed tones of focus group conversations treasured by deliberative democrats today, has a rich political history and a continuing relevance. This paper will focus on five performative modes for the communication of political ideas: the monologue, the dialogue, the oration, the interjection, and the noisy crowd. While this list may not be exhaustive, it will be used here as a starting point for further exploration. I will contend that in each of these performative modes, the communication of political ideas is framed by the noise of actual, or textually imagined kinds of political speech designed to underscore the validity of the ideas conveyed. One of the most important reasons for traversing this variable performative and acoustic terrain today is to enable us to hear and to listen to political speech amid the potentially polluting hum of political white noise.

Effects of alkalinity sources on the stability of anaerobic digestion from food waste.

Science.gov (United States)

Chen, Shujun; Zhang, Jishi; Wang, Xikui

2015-11-01

This study investigated the effects of some alkalinity sources on the stability of anaerobic digestion (AD) from food waste (FW). Four alkalinity sources, namely lime mud from papermaking (LMP), waste eggshell (WES), CaCO3 and NaHCO3, were applied as buffer materials and their stability effects were evaluated in batch AD. The results showed that LMP and CaCO3 had more remarkable effects than NaHCO3 and WES on FW stabilization. The methane yields were 120.2, 197.0, 156.2, 251.0 and 194.8 ml g(-1) VS for the control and synergistic digestions of CaCO3, NaHCO3, LMP and WES added into FW, respectively. The corresponding final alkalinity reached 5906, 7307, 9504, 7820 and 6782 mg l(-1), while the final acidities were determined to be 501, 200, 50, 350 and 250 mg l(-1), respectively. This indicated that the synergism between alkalinity and inorganic micronutrients from different alkalinity sources played an important role in the process stability of AD from FW. © The Author(s) 2015.

Whole-exome sequencing revealed two novel mutations in Usher syndrome.

Science.gov (United States)

Koparir, Asuman; Karatas, Omer Faruk; Atayoglu, Ali Timucin; Yuksel, Bayram; Sagiroglu, Mahmut Samil; Seven, Mehmet; Ulucan, Hakan; Yuksel, Adnan; Ozen, Mustafa

2015-06-01

Usher syndrome is a clinically and genetically heterogeneous autosomal recessive inherited disorder accompanied by hearing loss and retinitis pigmentosa (RP). Since the associated genes are various and quite large, we utilized whole-exome sequencing (WES) as a diagnostic tool to identify the molecular basis of Usher syndrome. DNA from a 12-year-old male diagnosed with Usher syndrome was analyzed by WES. Mutations detected were confirmed by Sanger sequencing. The pathogenicity of these mutations was determined by in silico analysis. A maternally inherited deleterious frameshift mutation, c.14439_14454del in exon 66 and a paternally inherited non-sense c.10830G>A stop-gain SNV in exon 55 of USH2A were found as two novel compound heterozygous mutations. Both of these mutations disrupt the C terminal of USH2A protein. As a result, WES revealed two novel compound heterozygous mutations in a Turkish USH2A patient. This approach gave us an opportunity to have an appropriate diagnosis and provide genetic counseling to the family within a reasonable time. Copyright © 2015 Elsevier B.V. All rights reserved.

Correlation between renew able energy source's energy output and load

International Nuclear Information System (INIS)

Ali, G.H.M.; El-Zeftawy, A.A.

1996-01-01

The common problem to all renew energy sources (RESs) is the mismatch between their energy output and load demand. In remote areas, the solution of this problem is in general employing a small diesel-generator or a storage battery. But, the storage battery is a major cost element of RESs and small diesel-generator is unreliable and costly. Therefore, a proposed technique has been introduced in this work to determine correlation between the energy output of wind energy systems (WES) and isolated loads. solar photovoltaic power system (PVS) and two of energy storage facilities are used here for this correlation. The proposed technique includes also two models for optimizing the generation and costs of WES accompanied with PVS, storage battery and water storage (reservoir) to accommodate an isolated load. The proposed technique is applied with the dynamic programming to coordinate the energy output of a WES with residential and pumping load in remote area of egypt. The results of this application reveal that minimization of both capacity of the storage battery and the whole power system cost are obtained. 4 figs

Wind Energy Solutions : to bring renewable energy everywhere

International Nuclear Information System (INIS)

Leeuw de, J.

2008-01-01

This presentation discussed smaller wind turbines designed by the Netherlands-based company Wind Energy Solutions (WES). Ranging between 2.5 kW and 250 kW, the smaller turbines are used in farming applications as well as for factories, in isolated communities, and by utilities with smaller electricity grids. The company also designs off-grid and stand-alone turbines; turbines with equal-sized generators; and turbines that do not require dumploads, batteries, or flywheels. WES turbines have been installed at farms, in parking lots, airports, gas stations, and on the grounds of large office buildings. The company advises that it is important to conduct initial surveys of the location for planned turbines before purchasing them. Legal and financial issues must also be explored, and wind speed data must be obtained in order to select an appropriate turbine. WES has also designed a range of control rooms, turbine cables, and remote monitoring devices for smaller wind turbines, as well as electronic microprocessors and inverters with PLC interfaces. Details of wind turbine installation procedures were included in this presentation. tabs., figs

Complex Landscape of Germline Variants in Brazilian Patients With Hereditary and Early Onset Breast Cancer

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Giovana T. Torrezan

2018-05-01

Full Text Available Pathogenic variants in known breast cancer (BC predisposing genes explain only about 30% of Hereditary Breast Cancer (HBC cases, whereas the underlying genetic factors for most families remain unknown. Here, we used whole-exome sequencing (WES to identify genetic variants associated to HBC in 17 patients of Brazil with familial BC and negative for causal variants in major BC risk genes (BRCA1/2, TP53, and CHEK2 c.1100delC. First, we searched for rare variants in 27 known HBC genes and identified two patients harboring truncating pathogenic variants in ATM and BARD1. For the remaining 15 negative patients, we found a substantial vast number of rare genetic variants. Thus, for selecting the most promising variants we used functional-based variant prioritization, followed by NGS validation, analysis in a control group, cosegregation analysis in one family and comparison with previous WES studies, shrinking our list to 23 novel BC candidate genes, which were evaluated in an independent cohort of 42 high-risk BC patients. Rare and possibly damaging variants were identified in 12 candidate genes in this cohort, including variants in DNA repair genes (ERCC1 and SXL4 and other cancer-related genes (NOTCH2, ERBB2, MST1R, and RAF1. Overall, this is the first WES study applied for identifying novel genes associated to HBC in Brazilian patients, in which we provide a set of putative BC predisposing genes. We also underpin the value of using WES for assessing the complex landscape of HBC susceptibility, especially in less characterized populations.

Insights from early experience of a Rare Disease Genomic Medicine Multidisciplinary Team: a qualitative study.

Science.gov (United States)

Ormondroyd, Elizabeth; Mackley, Michael P; Blair, Edward; Craft, Jude; Knight, Julian C; Taylor, John; Taylor, Jenny C; Wilkie, Andrew Om; Watkins, Hugh

2017-06-01

Whole-exome/whole-genome sequencing (WES/WGS) has the potential to enhance genetic diagnosis of rare disease, and is increasingly becoming part of routine clinical care in mainstream medicine. Effective translation will require ongoing efforts in a number of areas including: selection of appropriate patients, provision of effective consent, pre- and post-test genetic counselling, improving variant interpretation algorithms and practices, and management of secondary findings including those found incidentally and those actively sought. Allied to this is the need for an effective education programme for all members of clinical teams involved in care of patients with rare disease, as well as to maintain public confidence in the use of these technologies. We established a Genomic Medicine Multidisciplinary Team (GM-MDT) in 2014 to build on the experiences of earlier successful research-based WES/WGS studies, to address these needs and to review results including pertinent and secondary findings. Here we report on a qualitative study of decision-making in the GM-MDT combined with analysis of semi-structured interviews with GM-MDT members. Study findings show that members appreciate the clinical and scientific diversity of the GM-MDT and value it for education and oversight. To date, discussions have focussed on case selection including the extent and interpretation of clinical and family history information required to establish likely monogenic aetiology and inheritance model. Achieving a balance between effective use of WES/WGS - prioritising cases in a diverse and highly complex patient population where WES/WGS will be tractable - and meeting the recruitment targets of a large project is considered challenging.

New method for characterizing electron mediators in microbial systems using a thin-layer twin-working electrode cell.

Science.gov (United States)

Hassan, Md Mahamudul; Cheng, Ka Yu; Ho, Goen; Cord-Ruwisch, Ralf

2017-01-15

Microbial biofilms are significant ecosystems where the existence of redox gradients drive electron transfer often via soluble electron mediators. This study describes the use of two interfacing working electrodes (WEs) to simulate redox gradients within close proximity (250µm) for the detection and quantification of electron mediators. By using a common counter and reference electrode, the potentials of the two WEs were independently controlled to maintain a suitable "voltage window", which enabled simultaneous oxidation and reduction of electron mediators as evidenced by the concurrent anodic and cathodic currents, respectively. To validate the method, the electrochemical properties of different mediators (hexacyanoferrate, HCF, riboflavin, RF) were characterized by stepwise shifting the "voltage window" (ranging between 25 and 200mV) within a range of potentials after steady equilibrium current of both WEs was established. The resulting differences in electrical currents between the two WEs were recorded across a defined potential spectrum (between -1V and +0.5V vs. Ag/AgCl). Results indicated that the technique enabled identification (by the distinct peak locations at the potential scale) and quantification (by the peak of current) of the mediators for individual species as well as in an aqueous mixture. It enabled a precise determination of mid-potentials of the externally added mediators (HCF, RF) and mediators produced by pyocyanin-producing Pseudomonas aeruginosa (WACC 91) culture. The twin working electrode described is particularly suitable for studying mediator-dependent microbial electron transfer processes or simulating redox gradients as they exist in microbial biofilms. Copyright © 2016 Elsevier B.V. All rights reserved.

Exome sequencing in Jewish and Arab patients with rhabdomyolysis reveals single-gene etiology in 43% of cases.

Science.gov (United States)

Vivante, Asaf; Ityel, Hadas; Pode-Shakked, Ben; Chen, Jing; Shril, Shirlee; van der Ven, Amelie T; Mann, Nina; Schmidt, Johanna Magdalena; Segel, Reeval; Aran, Adi; Zeharia, Avraham; Staretz-Chacham, Orna; Bar-Yosef, Omer; Raas-Rothschild, Annick; Landau, Yuval E; Lifton, Richard P; Anikster, Yair; Hildebrandt, Friedhelm

2017-12-01

Rhabdomyolysis is a clinical emergency that may cause acute kidney injury (AKI). It can be acquired or due to monogenic mutations. Around 60 different rare monogenic forms of rhabdomyolysis have been reported to date. In the clinical setting, identifying the underlying molecular diagnosis is challenging due to nonspecific presentation, the high number of causative genes, and current lack of data on the prevalence of monogenic forms. We employed whole exome sequencing (WES) to reveal the percentage of rhabdomyolysis cases explained by single-gene (monogenic) mutations in one of 58 candidate genes. We investigated a cohort of 21 unrelated families with rhabdomyolysis, in whom no underlying etiology had been previously established. Using WES, we identified causative mutations in candidate genes in nine of the 21 families (43%). We detected disease-causing mutations in eight of 58 candidate genes, grouped into the following categories: (1) disorders of fatty acid metabolism (CPT2), (2) disorders of glycogen metabolism (PFKM and PGAM2), (3) disorders of abnormal skeletal muscle relaxation and contraction (CACNA1S, MYH3, RYR1 and SCN4A), and (4) disorders of purine metabolism (AHCY). Our findings demonstrate a very high detection rate for monogenic etiologies using WES and reveal broad genetic heterogeneity for rhabdomyolysis. These results highlight the importance of molecular genetic diagnostics for establishing an etiologic diagnosis. Because these patients are at risk for recurrent episodes of rhabdomyolysis and subsequent risk for AKI, WES allows adequate prophylaxis and treatment for these patients and their family members and enables a personalized medicine approach.

Coinheritance of biallelic SLURP1 and SLC39A4 mutations cause a severe genodermatosis with skin peeling and hair loss all over the body.

Science.gov (United States)

Harms, F L; Nampoothiri, S; Kortüm, F; Thomas, J; Panicker, V V; Alawi, M; Altmüller, J; Yesodharan, D; Kutsche, K

2018-06-27

Next-generation sequencing (NGS), especially multi-gene panels and whole-exome sequencing (WES), is a tool for identifying the cause of monogenic disorders and has played a role in uncovering the genetic cause of previously uncharacterized genodermatoses. 1 By the application of NGS, the concept of apparently novel or atypical clinical presentations has been challenged by the finding of two or more genetic diagnoses in affected individuals. Approximately 5% of cases in which WES was informative had dual or multiple molecular diagnoses. 2 This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Real time control of the SSC string magnets

International Nuclear Information System (INIS)

Calvo, O.; Flora, R.; MacPherson, M.

1987-01-01

The system described in this paper, called SECAR, was designed to control the excitation of a test string of magnets for the proposed Superconducting Super Collider (SSC) and will be used to upgrade the present Tevatron Excitation, Control and Regulation (TECAR) hardware and software. It resides in a VME orate and is controlled by a 68020/68881 based CPU running the application software under a real time operating system named VRTX

Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech.

Science.gov (United States)

Worthey, Elizabeth A; Raca, Gordana; Laffin, Jennifer J; Wilk, Brandon M; Harris, Jeremy M; Jakielski, Kathy J; Dimmock, David P; Strand, Edythe A; Shriberg, Lawrence D

2013-10-02

Childhood apraxia of speech (CAS) is a rare, severe, persistent pediatric motor speech disorder with associated deficits in sensorimotor, cognitive, language, learning and affective processes. Among other neurogenetic origins, CAS is the disorder segregating with a mutation in FOXP2 in a widely studied, multigenerational London family. We report the first whole-exome sequencing (WES) findings from a cohort of 10 unrelated participants, ages 3 to 19 years, with well-characterized CAS. As part of a larger study of children and youth with motor speech sound disorders, 32 participants were classified as positive for CAS on the basis of a behavioral classification marker using auditory-perceptual and acoustic methods that quantify the competence, precision and stability of a speaker's speech, prosody and voice. WES of 10 randomly selected participants was completed using the Illumina Genome Analyzer IIx Sequencing System. Image analysis, base calling, demultiplexing, read mapping, and variant calling were performed using Illumina software. Software developed in-house was used for variant annotation, prioritization and interpretation to identify those variants likely to be deleterious to neurodevelopmental substrates of speech-language development. Among potentially deleterious variants, clinically reportable findings of interest occurred on a total of five chromosomes (Chr3, Chr6, Chr7, Chr9 and Chr17), which included six genes either strongly associated with CAS (FOXP1 and CNTNAP2) or associated with disorders with phenotypes overlapping CAS (ATP13A4, CNTNAP1, KIAA0319 and SETX). A total of 8 (80%) of the 10 participants had clinically reportable variants in one or two of the six genes, with variants in ATP13A4, KIAA0319 and CNTNAP2 being the most prevalent. Similar to the results reported in emerging WES studies of other complex neurodevelopmental disorders, our findings from this first WES study of CAS are interpreted as support for heterogeneous genetic origins of

EVA: Exome Variation Analyzer, an efficient and versatile tool for filtering strategies in medical genomics

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Coutant Sophie

2012-09-01

Full Text Available Abstract Background Whole exome sequencing (WES has become the strategy of choice to identify a coding allelic variant for a rare human monogenic disorder. This approach is a revolution in medical genetics history, impacting both fundamental research, and diagnostic methods leading to personalized medicine. A plethora of efficient algorithms has been developed to ensure the variant discovery. They generally lead to ~20,000 variations that have to be narrow down to find the potential pathogenic allelic variant(s and the affected gene(s. For this purpose, commonly adopted procedures which implicate various filtering strategies have emerged: exclusion of common variations, type of the allelics variants, pathogenicity effect prediction, modes of inheritance and multiple individuals for exome comparison. To deal with the expansion of WES in medical genomics individual laboratories, new convivial and versatile software tools have to implement these filtering steps. Non-programmer biologists have to be autonomous combining themselves different filtering criteria and conduct a personal strategy depending on their assumptions and study design. Results We describe EVA (Exome Variation Analyzer, a user-friendly web-interfaced software dedicated to the filtering strategies for medical WES. Thanks to different modules, EVA (i integrates and stores annotated exome variation data as strictly confidential to the project owner, (ii allows to combine the main filters dealing with common variations, molecular types, inheritance mode and multiple samples, (iii offers the browsing of annotated data and filtered results in various interactive tables, graphical visualizations and statistical charts, (iv and finally offers export files and cross-links to external useful databases and softwares for further prioritization of the small subset of sorted candidate variations and genes. We report a demonstrative case study that allowed to identify a new candidate gene

Identification of Novel Variants in LTBP2 and PXDN Using Whole-Exome Sequencing in Developmental and Congenital Glaucoma.

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Shazia Micheal

Full Text Available Primary congenital glaucoma (PCG is the most common form of glaucoma in children. PCG occurs due to the developmental defects in the trabecular meshwork and anterior chamber of the eye. The purpose of this study is to identify the causative genetic variants in three families with developmental and primary congenital glaucoma (PCG with a recessive inheritance pattern.DNA samples were obtained from consanguineous families of Pakistani ancestry. The CYP1B1 gene was sequenced in the affected probands by conventional Sanger DNA sequencing. Whole exome sequencing (WES was performed in DNA samples of four individuals belonging to three different CYP1B1-negative families. Variants identified by WES were validated by Sanger sequencing.WES identified potentially causative novel mutations in the latent transforming growth factor beta binding protein 2 (LTBP2 gene in two PCG families. In the first family a novel missense mutation (c.4934G>A; p.Arg1645Glu co-segregates with the disease phenotype, and in the second family a novel frameshift mutation (c.4031_4032insA; p.Asp1345Glyfs*6 was identified. In a third family with developmental glaucoma a novel mutation (c.3496G>A; p.Gly1166Arg was identified in the PXDN gene, which segregates with the disease.We identified three novel mutations in glaucoma families using WES; two in the LTBP2 gene and one in the PXDN gene. The results will not only enhance our current understanding of the genetic basis of glaucoma, but may also contribute to a better understanding of the diverse phenotypic consequences caused by mutations in these genes.

Evaluating the Impacts of Climate Change on Soil Erosion Rates in Central Mexico

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Santos Martínez-Santiago

2017-07-01

Full Text Available Although water-eroded soil (WES resulting from human activities has been recognized as the leading global cause of land degradation, the soil erosion risks from climate change are not clear. Studies have reported that WES is the second most significant cause of soil loss in Mexico, and its future trajectory has not been sufficiently evaluated. The aims of this study are to 1 determine the impacts of climate change on WES and its distribution for the State of Aguascalientes, Mexico, and to 2 compare the present and future soil loss rates for the study unit (SU. The State of Aguascalientes is located in the “Region del Bajio.” The impact of climate change on WES was evaluated using the near-future divided world scenario (A2 presented in the IPCC Fourth Assessment Report. Daily temperature and precipitation data from 18 weather stations were downscaled to model historic laminar water erosion (HLWE and changes therein in the A2 near-future scenario for 2010–2039 (LWEScA2. Due to future changes in mean annual rainfall (MAR levels, a change in the LWEScA2 of between 1.6 and 8.9% could result in average soil losses up to 475.4 t ha-1 yr-1, representing a loss of slightly more than a 30-mm layer of mountain soil per year. The risk zones, classified as class 4 for LWE, are located to western of the State in part of municipalities of Calvillo, Jesus María, San José de Gracia y Cosio, where there are typical hills and falls with soil very sensitive to rain erosion.

Amplicon-based semiconductor sequencing of human exomes: performance evaluation and optimization strategies.

Science.gov (United States)

Damiati, E; Borsani, G; Giacopuzzi, Edoardo

2016-05-01

The Ion Proton platform allows to perform whole exome sequencing (WES) at low cost, providing rapid turnaround time and great flexibility. Products for WES on Ion Proton system include the AmpliSeq Exome kit and the recently introduced HiQ sequencing chemistry. Here, we used gold standard variants from GIAB consortium to assess the performances in variants identification, characterize the erroneous calls and develop a filtering strategy to reduce false positives. The AmpliSeq Exome kit captures a large fraction of bases (>94 %) in human CDS, ClinVar genes and ACMG genes, but with 2,041 (7 %), 449 (13 %) and 11 (19 %) genes not fully represented, respectively. Overall, 515 protein coding genes contain hard-to-sequence regions, including 90 genes from ClinVar. Performance in variants detection was maximum at mean coverage >120×, while at 90× and 70× we measured a loss of variants of 3.2 and 4.5 %, respectively. WES using HiQ chemistry showed ~71/97.5 % sensitivity, ~37/2 % FDR and ~0.66/0.98 F1 score for indels and SNPs, respectively. The proposed low, medium or high-stringency filters reduced the amount of false positives by 10.2, 21.2 and 40.4 % for indels and 21.2, 41.9 and 68.2 % for SNP, respectively. Amplicon-based WES on Ion Proton platform using HiQ chemistry emerged as a competitive approach, with improved accuracy in variants identification. False-positive variants remain an issue for the Ion Torrent technology, but our filtering strategy can be applied to reduce erroneous variants.

Human tear film and meibum. Very long chain wax esters and (O-acyl)-omega-hydroxy fatty acids of meibum

OpenAIRE

Butovich, Igor A.; Wojtowicz, Jadwiga C.; Molai, Mike

2009-01-01

Human meibum was targetly analyzed for the presence of intact wax esters (WEs) and related compounds by means of reverse-phase HPLC in combination with ion trap mass spectrometry. The major detected WEs were based on C18:n (n = 1–4) unsaturated FAs ranking in the following order of abundance: C18:1>C18:2>C18:3>C18:4. The major fatty alcohols (FAls) found in WE were of saturated nature and varied from C18:0 to C28:0. The three most abundant species were C18:1-FA esters of C24:0, C25:0, and C26...

HABP2 p.G534E variant in patients with family history of thyroid and breast cancer

DEFF Research Database (Denmark)

Pinheiro, Maísa; Drigo, Sandra Aparecida; Tonhosolo, Renata

2017-01-01

Familial Papillary Thyroid Carcinoma (PTC) has been described as a hereditary predisposition cancer syndrome associated with mutations in candidate genes including HABP2. Two of 20 probands from families with history of PTC and breast carcinoma (BC) were evaluated by whole exome sequencing (WES...... familial PTC cases. Genes potentially associated with deregulation of the extracellular matrix organization pathway (CTSB, TNXB, COL4A3, COL16A1, COL24A1, COL5A2, NID1, LOXL2, MMP11, TRIM24 and MUSK) and DNA repair function (NBN and MSH2) were detected by WES, suggesting that other cancer-associated genes...

DEMOCRACY AND DEVELOPMENT IN WEsT AFRicA: How ...

African Journals Online (AJOL)

that can be pursued to help meet the challenges of constructing democratic development at the ... Soviet Union and, more recently, by a number of South ... America. Gerray, Thacker and Affaro. (2006) in a new study have argued that from a ... during the cold war, western governments ... attention because of their strategic.

High tide in the Delta

International Nuclear Information System (INIS)

Vellinga, P.

2008-01-01

This inaugural speech takes a closer look at the relation of the Netherlands with water and sea. The author pleas for better connections of land and water and better connections of fresh and salt water. The oration discusses the influence of man on the climate, recent discoveries in the field of climate, urgency in the field of energy, opportunities for high tide protection in the Netherlands and plans for filling the new chair [nl

The Ethics of Military Deception

Science.gov (United States)

1998-06-05

comment directly on the moral dimensions of military deception is the great Roman orator, Marcus Tullius Cicero (106-43 B.C.). Of paramount...action is to be commended, if what is 1 Marcus Tullius Cicero, De Officiis, I.xiii.40, trans. Walter Miller (Cambridge: Harvard University Press, 1913... Aurelius Augustinus (A.D. 354-430), later known as Saint Augustine, the Catholic bishop of Hippo in North Africa, is in many ways the pivotal

Targeted/exome sequencing identified mutations in ten Chinese patients diagnosed with Noonan syndrome and related disorders

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Shanshan Xu

2017-10-01

Full Text Available Abstract Background Noonan syndrome (NS and Noonan syndrome with multiple lentigines (NSML are autosomal dominant developmental disorders. NS and NSML are caused by abnormalities in genes that encode proteins related to the RAS-MAPK pathway, including PTPN11, RAF1, BRAF, and MAP2K. In this study, we diagnosed ten NS or NSML patients via targeted sequencing or whole exome sequencing (TS/WES. Methods TS/WES was performed to identify mutations in ten Chinese patients who exhibited the following manifestations: potential facial dysmorphisms, short stature, congenital heart defects, and developmental delay. Sanger sequencing was used to confirm the suspected pathological variants in the patients and their family members. Results TS/WES revealed three mutations in the PTPN11 gene, three mutations in RAF1 gene, and four mutations in BRAF gene in the NS and NSML patients who were previously diagnosed based on the abovementioned clinical features. All the identified mutations were determined to be de novo mutations. However, two patients who carried the same mutation in the RAF1 gene presented different clinical features. One patient with multiple lentigines was diagnosed with NSML, while the other patient without lentigines was diagnosed with NS. In addition, a patient who carried a hotspot mutation in the BRAF gene was diagnosed with NS instead of cardiofaciocutaneous syndrome (CFCS. Conclusions TS/WES has emerged as a useful tool for definitive diagnosis and accurate genetic counseling of atypical cases. In this study, we analyzed ten Chinese patients diagnosed with NS and related disorders and identified their correspondingPTPN11, RAF1, and BRAF mutations. Among the target genes, BRAF showed the same degree of correlation with NS incidence as that of PTPN11 or RAF1.

Evaluation of the influence exerted by different dental specialty backgrounds and measuring instrument reproducibility on esthetic aspects of maxillary implant-supported single crown.

Science.gov (United States)

Vaidya, Samriddhi; Ho, Yu Lau Elaine; Hao, Jie; Lang, Niklaus P; Mattheos, Nikos

2015-03-01

To evaluate the influence exerted by different dental specialty backgrounds as well as the validity and reproducibility of the Pink Esthetic Score/White Esthetic Score (PES/WES) and the modified Implant Crown Aesthetic Index (mod-ICAI) on the assessment of esthetic aspects of maxillary implants supported single-tooth prosthesis. A total of fourteen examiners (Two orthodontists, two prosthodontists, two oral surgeons, two periodontists, two dental technicians, two dental assistants, and two postgraduate students in Implant Dentistry evaluated 20 photographs of single-implant-supported crowns and five photographs of unrestored teeth of esthetic zone in a two part study. The examiners assessed the photographs with each index (Pink Esthetic Score/White Esthetic Score and modified Implant Crown Aesthetic Index), twice with a week's interval. Orders of photographs were rearranged in the second assessment. Kruskal-Wallis test results showed significant differences among all the six specialties (P ≤ 0.001). DAs and periodontists had significantly better ratings than other specialties with both indices. Prosthodontists had the lowest mean rank scores regardless of the index. Interobserver agreement was also lowest between the two prosthodontists (4-28%), rest of the groups had low-to-moderate agreement (20-80%) when limited allowance was accepted. With mod-ICAI, more interobserver agreement was noted within the specialty group than with PES/WES. The PES/WES and the modified ICAI can be reliable estimates of esthetic outcomes. The assessor degree of specialization affected the esthetic evaluation with both the PES/WES and the modified ICAI. DAs and periodontists were identified to provide more favorable ratings than other specialties while prosthodontists were most critical in this study. With modified ICAI, more interobserver agreement within specialty resulted. The interexaminer agreement may be increased if more tolerance of 1-2 points is considered. © 2014 John Wiley

Whole-Exome Sequencing in Adults With Chronic Kidney Disease: A Pilot Study.

Science.gov (United States)

Lata, Sneh; Marasa, Maddalena; Li, Yifu; Fasel, David A; Groopman, Emily; Jobanputra, Vaidehi; Rasouly, Hila; Mitrotti, Adele; Westland, Rik; Verbitsky, Miguel; Nestor, Jordan; Slater, Lindsey M; D'Agati, Vivette; Zaniew, Marcin; Materna-Kiryluk, Anna; Lugani, Francesca; Caridi, Gianluca; Rampoldi, Luca; Mattoo, Aditya; Newton, Chad A; Rao, Maya K; Radhakrishnan, Jai; Ahn, Wooin; Canetta, Pietro A; Bomback, Andrew S; Appel, Gerald B; Antignac, Corinne; Markowitz, Glen S; Garcia, Christine K; Kiryluk, Krzysztof; Sanna-Cherchi, Simone; Gharavi, Ali G

2018-01-16

The utility of whole-exome sequencing (WES) for the diagnosis and management of adult-onset constitutional disorders has not been adequately studied. Genetic diagnostics may be advantageous in adults with chronic kidney disease (CKD), in whom the cause of kidney failure often remains unknown. To study the diagnostic utility of WES in a selected referral population of adults with CKD. Observational cohort. A major academic medical center. 92 adults with CKD of unknown cause or familial nephropathy or hypertension. The diagnostic yield of WES and its potential effect on clinical management. Whole-exome sequencing provided a diagnosis in 22 of 92 patients (24%), including 9 probands with CKD of unknown cause and encompassing 13 distinct genetic disorders. Among these, loss-of-function mutations were identified in PARN in 2 probands with tubulointerstitial fibrosis. PARN mutations have been implicated in a short telomere syndrome characterized by lung, bone marrow, and liver fibrosis; these findings extend the phenotype of PARN mutations to renal fibrosis. In addition, review of the American College of Medical Genetics actionable genes identified a pathogenic BRCA2 mutation in a proband who was diagnosed with breast cancer on follow-up. The results affected clinical management in most identified cases, including initiation of targeted surveillance, familial screening to guide donor selection for transplantation, and changes in therapy. The small sample size and recruitment at a tertiary care academic center limit generalizability of findings among the broader CKD population. Whole-exome sequencing identified diagnostic mutations in a substantial number of adults with CKD of many causes. Further study of the utility of WES in the evaluation and care of patients with CKD in additional settings is warranted. New York State Empire Clinical Research Investigator Program, Renal Research Institute, and National Human Genome Research Institute of the National Institutes of

Whole-exome sequencing identifies novel MPL and JAK2 mutations in triple-negative myeloproliferative neoplasms.

Science.gov (United States)

Milosevic Feenstra, Jelena D; Nivarthi, Harini; Gisslinger, Heinz; Leroy, Emilie; Rumi, Elisa; Chachoua, Ilyas; Bagienski, Klaudia; Kubesova, Blanka; Pietra, Daniela; Gisslinger, Bettina; Milanesi, Chiara; Jäger, Roland; Chen, Doris; Berg, Tiina; Schalling, Martin; Schuster, Michael; Bock, Christoph; Constantinescu, Stefan N; Cazzola, Mario; Kralovics, Robert

2016-01-21

Essential thrombocythemia (ET) and primary myelofibrosis (PMF) are chronic diseases characterized by clonal hematopoiesis and hyperproliferation of terminally differentiated myeloid cells. The disease is driven by somatic mutations in exon 9 of CALR or exon 10 of MPL or JAK2-V617F in >90% of the cases, whereas the remaining cases are termed "triple negative." We aimed to identify the disease-causing mutations in the triple-negative cases of ET and PMF by applying whole-exome sequencing (WES) on paired tumor and control samples from 8 patients. We found evidence of clonal hematopoiesis in 5 of 8 studied cases based on clonality analysis and presence of somatic genetic aberrations. WES identified somatic mutations in 3 of 8 cases. We did not detect any novel recurrent somatic mutations. In 3 patients with clonal hematopoiesis analyzed by WES, we identified a somatic MPL-S204P, a germline MPL-V285E mutation, and a germline JAK2-G571S variant. We performed Sanger sequencing of the entire coding region of MPL in 62, and of JAK2 in 49 additional triple-negative cases of ET or PMF. New somatic (T119I, S204F, E230G, Y591D) and 1 germline (R321W) MPL mutation were detected. All of the identified MPL mutations were gain-of-function when analyzed in functional assays. JAK2 variants were identified in 5 of 57 triple-negative cases analyzed by WES and Sanger sequencing combined. We could demonstrate that JAK2-V625F and JAK2-F556V are gain-of-function mutations. Our results suggest that triple-negative cases of ET and PMF do not represent a homogenous disease entity. Cases with polyclonal hematopoiesis might represent hereditary disorders. © 2016 by The American Society of Hematology.

Diagnostic strategy in segmentation defect of the vertebrae: a retrospective study of 73 patients.

Science.gov (United States)

Lefebvre, Mathilde; Dieux-Coeslier, Anne; Baujat, Geneviève; Schaefer, Elise; Judith, Saint-Onge; Bazin, Anne; Pinson, Lucile; Attie-Bitach, Tania; Baumann, Clarisse; Fradin, Melanie; Pierquin, Genevieve; Julia, Sophie; Quélin, Chloé; Doray, Bérénice; Berg, Sylvie; Vincent-Delorme, Catherine; Lambert, Laetitia; Bachmann, Nadine; Lacombe, Didier; Isidor, Bertrand; Laurent, Nicole; Joelle, Roume; Blanchet, Patricia; Odent, Sylvie; Kervran, Dominique; Leporrier, Nathalie; Abel, Carine; Segers, Karine; Guiliano, Fabienne; Ginglinger-Fabre, Emmanuelle; Selicorni, Angelo; Goldenberg, Alice; El Chehadeh, Salima; Francannet, Christine; Demeer, Benedicte; Duffourd, Yannis; Thauvin-Robinet, Christel; Verloes, Alain; Cormier-Daire, Valerie; Riviere, Jean Baptiste; Faivre, Laurence; Thevenon, Julien

2018-02-19

Segmentation defects of the vertebrae (SDV) are non-specific features found in various syndromes. The molecular bases of SDV are not fully elucidated due to the wide range of phenotypes and classification issues. The genes involved are in the Notch signalling pathway, which is a key system in somitogenesis. Here we report on mutations identified in a diagnosis cohort of SDV. We focused on spondylocostal dysostosis (SCD) and the phenotype of these patients in order to establish a diagnostic strategy when confronted with SDV. We used DNA samples from a cohort of 73 patients and performed targeted sequencing of the five known SCD-causing genes ( DLL3 , MESP2 , LFNG , HES7 and TBX6 ) in the first 48 patients and whole-exome sequencing (WES) in 28 relevant patients. Ten diagnoses, including four biallelic variants in TBX6 , two biallelic variants in LFNG and DLL3 , and one in MESP2 and HES7 , were made with the gene panel, and two diagnoses, including biallelic variants in FLNB and one variant in MEOX1, were made by WES. The diagnostic yield of the gene panel was 10/73 (13.7%) in the global cohort but 8/10 (80%) in the subgroup meeting the SCD criteria; the diagnostic yield of WES was 2/28 (8%). After negative array CGH, targeted sequencing of the five known SCD genes should only be performed in patients who meet the diagnostic criteria of SCD. The low proportion of candidate genes identified by WES in our cohort suggests the need to consider more complex genetic architectures in cases of SDV. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Portero versus portador: Spanish interpretation of genomic terminology during whole exome sequencing results disclosure.

Science.gov (United States)

Gutierrez, Amanda M; Robinson, Jill O; Statham, Emily E; Scollon, Sarah; Bergstrom, Katie L; Slashinski, Melody J; Parsons, Donald W; Plon, Sharon E; McGuire, Amy L; Street, Richard L

2017-11-01

Describe modifications to technical genomic terminology made by interpreters during disclosure of whole exome sequencing (WES) results. Using discourse analysis, we identified and categorized interpretations of genomic terminology in 42 disclosure sessions where Spanish-speaking parents received their child's WES results either from a clinician using a medical interpreter, or directly from a bilingual physician. Overall, 76% of genomic terms were interpreted accordantly, 11% were misinterpreted and 13% were omitted. Misinterpretations made by interpreters and bilingual physicians included using literal and nonmedical terminology to interpret genomic concepts. Modifications to genomic terminology made during interpretation highlight the need to standardize bilingual genomic lexicons. We recommend Spanish terms that can be used to refer to genomic concepts.

Enabling technologies and methods for the retro-fitting of AI software into NPPS

International Nuclear Information System (INIS)

Pymm, P.

1994-01-01

Scottish Nuclear have a number of plant monitoring and training applications at their operational nuclear power plant which could benefit from the introduction of artificial intelligence (AI) software. An outline of early work on two current AI developments in the areas of advanced operator aids and intelligent training is given. A generic workstation based engineering simulator (WES) which provides a prototyping environment for AI product application development and evaluation and development of human-computer interface (HCI) designs for plant installation is described. It is concluded that the WES architecture facilitates both migration of the prototype AI application to the plant and collaboration in the AI field between Scottish Nuclear and other organizations. (author). 1 ref., 6 figs

Molecular Diagnostic Experience of Whole-Exome Sequencing in Adult Patients

Science.gov (United States)

Posey, Jennifer E.; Rosenfeld, Jill A.; James, Regis A.; Bainbridge, Matthew; Niu, Zhiyv; Wang, Xia; Dhar, Shweta; Wiszniewski, Wojciech; Akdemir, Zeynep H.C.; Gambin, Tomasz; Xia, Fan; Person, Richard E.; Walkiewicz, Magdalena; Shaw, Chad A.; Sutton, V. Reid; Beaudet, Arthur L.; Muzny, Donna; Eng, Christine M.; Yang, Yaping; Gibbs, Richard A.; Lupski, James R.; Boerwinkle, Eric; Plon, Sharon E.

2015-01-01

Purpose Whole exome sequencing (WES) is increasingly used as a diagnostic tool in medicine, but prior reports focus on predominantly pediatric cohorts with neurologic or developmental disorders. We describe the diagnostic yield and characteristics of whole exome sequencing in adults. Methods We performed a retrospective analysis of consecutive WES reports for adults from a diagnostic laboratory. Phenotype composition was determined using Human Phenotype Ontology terms. Results Molecular diagnoses were reported for 17.5% (85/486) of adults, lower than a primarily pediatric population (25.2%; p=0.0003); the diagnostic rate was higher (23.9%) in those 18–30 years of age compared to patients over 30 years (10.4%; p=0.0001). Dual Mendelian diagnoses contributed to 7% of diagnoses, revealing blended phenotypes. Diagnoses were more frequent among individuals with abnormalities of the nervous system, skeletal system, head/neck, and growth. Diagnostic rate was independent of family history information, and de novo mutations contributed to 61.4% of autosomal dominant diagnoses. Conclusion Early WES experience in adults demonstrates molecular diagnoses in a substantial proportion of patients, informing clinical management, recurrence risk and recommendations for relatives. A positive family history was not predictive, consistent with molecular diagnoses often revealed by de novo events, informing the Mendelian basis of genetic disease in adults. PMID:26633545

Identification of the PLA2G6 c.1579G>A Missense Mutation in Papillon Dog Neuroaxonal Dystrophy Using Whole Exome Sequencing Analysis.

Directory of Open Access Journals (Sweden)

Masaya Tsuboi

Full Text Available Whole exome sequencing (WES has become a common tool for identifying genetic causes of human inherited disorders, and it has also recently been applied to canine genome research. We conducted WES analysis of neuroaxonal dystrophy (NAD, a neurodegenerative disease that sporadically occurs worldwide in Papillon dogs. The disease is considered an autosomal recessive monogenic disease, which is histopathologically characterized by severe axonal swelling, known as "spheroids," throughout the nervous system. By sequencing all eleven DNA samples from one NAD-affected Papillon dog and her parents, two unrelated NAD-affected Papillon dogs, and six unaffected control Papillon dogs, we identified 10 candidate mutations. Among them, three candidates were determined to be "deleterious" by in silico pathogenesis evaluation. By subsequent massive screening by TaqMan genotyping analysis, only the PLA2G6 c.1579G>A mutation had an association with the presence or absence of the disease, suggesting that it may be a causal mutation of canine NAD. As a human homologue of this gene is a causative gene for infantile neuroaxonal dystrophy, this canine phenotype may serve as a good animal model for human disease. The results of this study also indicate that WES analysis is a powerful tool for exploring canine hereditary diseases, especially in rare monogenic hereditary diseases.

Lessons learned from whole exome sequencing in multiplex families affected by a complex genetic disorder, intracranial aneurysm.

Directory of Open Access Journals (Sweden)

Janice L Farlow

Full Text Available Genetic risk factors for intracranial aneurysm (IA are not yet fully understood. Genomewide association studies have been successful at identifying common variants; however, the role of rare variation in IA susceptibility has not been fully explored. In this study, we report the use of whole exome sequencing (WES in seven densely-affected families (45 individuals recruited as part of the Familial Intracranial Aneurysm study. WES variants were prioritized by functional prediction, frequency, predicted pathogenicity, and segregation within families. Using these criteria, 68 variants in 68 genes were prioritized across the seven families. Of the genes that were expressed in IA tissue, one gene (TMEM132B was differentially expressed in aneurysmal samples (n=44 as compared to control samples (n=16 (false discovery rate adjusted p-value=0.023. We demonstrate that sequencing of densely affected families permits exploration of the role of rare variants in a relatively common disease such as IA, although there are important study design considerations for applying sequencing to complex disorders. In this study, we explore methods of WES variant prioritization, including the incorporation of unaffected individuals, multipoint linkage analysis, biological pathway information, and transcriptome profiling. Further studies are needed to validate and characterize the set of variants and genes identified in this study.

Comparison of Pharmaceutical, Psychological, and Exercise Treatments for Cancer-Related Fatigue: A Meta-analysis.

Science.gov (United States)

Mustian, Karen M; Alfano, Catherine M; Heckler, Charles; Kleckner, Amber S; Kleckner, Ian R; Leach, Corinne R; Mohr, David; Palesh, Oxana G; Peppone, Luke J; Piper, Barbara F; Scarpato, John; Smith, Tenbroeck; Sprod, Lisa K; Miller, Suzanne M

2017-07-01

Cancer-related fatigue (CRF) remains one of the most prevalent and troublesome adverse events experienced by patients with cancer during and after therapy. To perform a meta-analysis to establish and compare the mean weighted effect sizes (WESs) of the 4 most commonly recommended treatments for CRF-exercise, psychological, combined exercise and psychological, and pharmaceutical-and to identify independent variables associated with treatment effectiveness. PubMed, PsycINFO, CINAHL, EMBASE, and the Cochrane Library were searched from the inception of each database to May 31, 2016. Randomized clinical trials in adults with cancer were selected. Inclusion criteria consisted of CRF severity as an outcome and testing of exercise, psychological, exercise plus psychological, or pharmaceutical interventions. Studies were independently reviewed by 12 raters in 3 groups using a systematic and blinded process for reconciling disagreement. Effect sizes (Cohen d) were calculated and inversely weighted by SE. Severity of CRF was the primary outcome. Study quality was assessed using a modified 12-item version of the Physiotherapy Evidence-Based Database scale (range, 0-12, with 12 indicating best quality). From 17 033 references, 113 unique studies articles (11 525 unique participants; 78% female; mean age, 54 [range, 35-72] years) published from January 1, 1999, through May 31, 2016, had sufficient data. Studies were of good quality (mean Physiotherapy Evidence-Based Database scale score, 8.2; range, 5-12) with no evidence of publication bias. Exercise (WES, 0.30; 95% CI, 0.25-0.36; P psychological (WES, 0.27; 95% CI, 0.21-0.33; P psychological interventions (WES, 0.26; 95% CI, 0.13-0.38; P psychological mode, type of control condition, use of intention-to-treat analysis, and fatigue measures (WES range, -0.91 to 0.99). Results suggest that the effectiveness of behavioral interventions, specifically exercise and psychological interventions, is not attributable to

Antibacterial activity of the sponge Ircinia ramosa: Importance of its surface-associated bacteria

Digital Repository Service at National Institute of Oceanography (India)

Thakur, N.L.; Anil, A.C.

, and concentrated under reduced pressure in a rotary evap- orator. A flow chart of extraction of sponge and its associated bacteria and anti- bacterial bioassays is given in Figure 1. Fractionation of Crude Extracts. The crude methanol extracts collected during... activity, and (3) whether there is a role for sponge surface-associated bacteria in antibacterial activity of the host? ANTIBACTERIAL ACTIVITY OF SPONGE 59 METHODS AND MATERIALS Specimen Collection and Preparation of Crude Extracts. Specimens of Ircinia...

From Pericles to Plato

DEFF Research Database (Denmark)

Larsen, Øjvind

2012-01-01

Plato is normally taken as one of the founders of Western political philosophy, not at least with his Republic. Here, he constructs a hierarchy of forms of governments, beginning with aristocracy at the top as a critical standard for the other forms of governments, and proceeding through timocracy......’ funeral oration is used to show that Pericles presented a democratic political philosophy that can serve as a counterpoint to Plato’s political philosophy in the Republic....

A KAS2 cDNA complements the phenotypes of the Arabidopsis fab1 mutant that differs in a single residue bordering the substrate binding pocket

DEFF Research Database (Denmark)

Carlsson, A.S.; LaBrie, S.T.; Kinney, A.J.

2002-01-01

The fab1 mutant of Arabidopsis is partially deficient in activity of ß-ketoacyl-[acyl carrier protein] synthase II (KAS II). This defect results in increased levels of 16 : 0 fatty acid and is associated with damage and death of the mutants at low temperature. Transformation of fab1 plants with a c......DNA from Brassica napus encoding a KAS II enzyme resulted in complementation of both mutant phenotypes. The dual complementation by expression of the single gene proves that low-temperature damage is a consequence of altered membrane unsaturation. The fab1 mutation is a single nucleotide change...... chain to bend. For functional analysis the equivalent Leu207Phe mutation was introduced into the fabB gene encoding the E. coli KAS I enzyme. Compared to wild-type, the Leu207Phe protein showed a 10-fold decrease in binding affinity for the fatty acid substrate, exhibited a modified behavior during size...

Initial Earthquake Centrifuge Model Experiments for the Study of Liquefaction

National Research Council Canada - National Science Library

Steedman, R

1998-01-01

.... These are intended to gather data suitable for the development of improved design approaches for the prediction of liquefaction under earthquake loading using the new centrifuge facility at the WES...

Solid polymer electrolyte water electrolysis system development. [to generate oxygen for manned space station applications

Science.gov (United States)

1975-01-01

Solid polymer electrolyte technology used in a water electrolysis system (WES) to generate oxygen and hydrogen for manned space station applications was investigated. A four-man rated, low pressure breadboard water electrolysis system with the necessary instrumentation and controls was fabricated and tested. A six man rated, high pressure, high temperature, advanced preprototype WES was developed. This configuration included the design and development of an advanced water electrolysis module, capable of operation at 400 psig and 200 F, and a dynamic phase separator/pump in place of a passive phase separator design. Evaluation of this system demonstrated the goal of safe, unattended automated operation at high pressure and high temperature with an accumulated gas generation time of over 1000 hours.

Our underpinnings: a bicentennial view. The 1975 Harvey Cushing oration.

Science.gov (United States)

McCracken, P W

1975-11-01

The author describes the emergence of the liberal traditions which is the foundation of the political and economic systems in this country and considers policies that may affect our social and economic future.

Hazardous Waste Research Center

Data.gov (United States)

Federal Laboratory Consortium — The U.S. Army Engineer Waterways Experiment Station (WES) is playing a major role in development of technologies for cleanup of toxic and hazardous waste in military...

Meteorología clásica en imágenes de la última época de la Antigüedad, ilustrada con ejemplos sacados de Gregorio Nacianceno

OpenAIRE

Kertsch, Manfred

1980-01-01

Using the imagery of Gregory of Nazianzus as starting point, the author tries to show that the doxographical example in Gregory’s Second Theological Oration (Or. XXVIII 26, PG 36, 61 C-64A), in combination with several other similar specimina, furnished by late Antiquity, may help resolve the problem raised by Quidam existimant at Seneca, Natur. quaest. III 24, 4. Who is meant here by quidam? In the author’s opinion: primarily Posidonius. In addition, this paper stresses the general significa...

Nonlinear Frequency Conversion in III-V Semiconductor Photonic Crystals

Science.gov (United States)

2012-03-01

benefited early in my PhD from the assistance of Dirk Englund and Vanessa Sih. Subsequently, I was fortunate to collab- orate with newer members of the...to defense practice talks. I would also like to acknowledge Seth Lloyd, Vicky Wen, Jason Pelc, Qiang Zhang, Peter McMahon, Liz Edwards , Stephanie...2006. [67] Z. Yang, P. Chak, A. D. Bristow, H. M. van Driel, R. Iyer, J. S. Aitchison, A. L. Smirl, and J. E. Sipe, “Enhanced second-harmonic

Options for In Situ Capping of Palos Verdes Shelf Contaminated Sediments

National Research Council Canada - National Science Library

Palermo, Michael; Schroeder, Paul; Rivera, Yilda; Ruiz, Carlos; Clarke, Doug; Gailani, Joe; Clausner, James; Hynes, Mary; Fredette, Thomas; Tardy, Barbara

1999-01-01

The U.S. Army Engineer Waterways Experiment Station (WES) has performed an evaluation of in situ capping options for sediment restoration of DDT and PCB contaminated sediments on the Palos Verdes (PV...

Novel rare missense variations and risk of autism spectrum disorder: whole-exome sequencing in two families with affected siblings and a two-stage follow-up study in a Japanese population.

Directory of Open Access Journals (Sweden)

Jun Egawa

Full Text Available Rare inherited variations in multiplex families with autism spectrum disorder (ASD are suggested to play a major role in the genetic etiology of ASD. To further investigate the role of rare inherited variations, we performed whole-exome sequencing (WES in two families, each with three affected siblings. We also performed a two-stage follow-up case-control study in a Japanese population. WES of the six affected siblings identified six novel rare missense variations. Among these variations, CLN8 R24H was inherited in one family by three affected siblings from an affected father and thus co-segregated with ASD. In the first stage of the follow-up study, we genotyped the six novel rare missense variations identified by WES in 241 patients and 667 controls (the Niigata sample. Only CLN8 R24H had higher mutant allele frequencies in patients (1/482 compared with controls (1/1334. In the second stage, this variation was further genotyped, yet was not detected in a sample of 309 patients and 350 controls (the Nagoya sample. In the combined Niigata and Nagoya samples, there was no significant association (odds ratio = 1.8, 95% confidence interval = 0.1-29.6. These results suggest that CLN8 R24H plays a role in the genetic etiology of ASD, at least in a subset of ASD patients.

Wood nitrogen concentrations in tropical trees: phylogenetic patterns and ecological correlates.

Science.gov (United States)

Martin, Adam R; Erickson, David L; Kress, W John; Thomas, Sean C

2014-11-01

In tropical and temperate trees, wood chemical traits are hypothesized to covary with species' life-history strategy along a 'wood economics spectrum' (WES), but evidence supporting these expected patterns remains scarce. Due to its role in nutrient storage, we hypothesize that wood nitrogen (N) concentration will covary along the WES, being higher in slow-growing species with high wood density (WD), and lower in fast-growing species with low WD. In order to test this hypothesis we quantified wood N concentrations in 59 Panamanian hardwood species, and used this dataset to examine ecological correlates and phylogenetic patterns of wood N. Wood N varied > 14-fold among species between 0.04 and 0.59%; closely related species were more similar in wood N than expected by chance. Wood N was positively correlated with WD, and negatively correlated with log-transformed relative growth rates, although these relationships were relatively weak. We found evidence for co-evolution between wood N and both WD and log-transformed mortality rates. Our study provides evidence that wood N covaries with tree life-history parameters, and that these patterns consistently co-evolve in tropical hardwoods. These results provide some support for the hypothesized WES, and suggest that wood is an increasingly important N pool through tropical forest succession. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Targeted gene panel sequencing in children with very early onset inflammatory bowel disease--evaluation and prospective analysis.

Science.gov (United States)

Kammermeier, Jochen; Drury, Suzanne; James, Chela T; Dziubak, Robert; Ocaka, Louise; Elawad, Mamoun; Beales, Philip; Lench, Nicholas; Uhlig, Holm H; Bacchelli, Chiara; Shah, Neil

2014-11-01

Multiple monogenetic conditions with partially overlapping phenotypes can present with inflammatory bowel disease (IBD)-like intestinal inflammation. With novel genotype-specific therapies emerging, establishing a molecular diagnosis is becoming increasingly important. We have introduced targeted next-generation sequencing (NGS) technology as a prospective screening tool in children with very early onset IBD (VEOIBD). We evaluated the coverage of 40 VEOIBD genes in two separate cohorts undergoing targeted gene panel sequencing (TGPS) (n=25) and whole exome sequencing (WES) (n=20). TGPS revealed causative mutations in four genes (IL10RA, EPCAM, TTC37 and SKIV2L) discovered unexpected phenotypes and directly influenced clinical decision making by supporting as well as avoiding haematopoietic stem cell transplantation. TGPS resulted in significantly higher median coverage when compared with WES, fewer coverage deficiencies and improved variant detection across established VEOIBD genes. Excluding or confirming known VEOIBD genotypes should be considered early in the disease course in all cases of therapy-refractory VEOIBD, as it can have a direct impact on patient management. To combine both described NGS technologies would compensate for the limitations of WES for disease-specific application while offering the opportunity for novel gene discovery in the research setting. 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.

Mutations in Plasmalemma Vesicle Associated Protein Result in Sieving Protein-Losing Enteropathy Characterized by Hypoproteinemia, Hypoalbuminemia, and HypertriglyceridemiaSummary

Directory of Open Access Journals (Sweden)

Abdul Elkadri

2015-07-01

Full Text Available Background & Aims: Severe intestinal diseases observed in very young children are often the result of monogenic defects. We used whole-exome sequencing (WES to examine genetics in a patient with a distinct severe form of protein-losing enteropathy (PLE characterized by hypoproteinemia, hypoalbuminemia, and hypertriglyceridemia. Methods: WES was performed at the Centre for Applied Genomics, Hospital for Sick Children, Toronto, Canada, and exome library preparation was performed with the Ion Torrent AmpliSeq RDY Exome Kit. Functional studies were based on the identified mutation. Results: Using WES we identified a homozygous nonsense mutation (1072C>T; p.Arg358* in the PLVAP (plasmalemma vesicle-associated protein gene in an infant from consanguineous parents who died at 5 months of age of severe PLE. Functional studies determined that the mutated PLVAP mRNA and protein were not expressed in the patient biopsy tissues, presumably secondary to nonsense-mediated mRNA decay. Pathological analysis showed that the loss of PLVAP resulted in disruption of endothelial fenestrated diaphragms. Conclusions: The PLVAP p.Arg358* mutation resulted in the loss of PLVAP expression with subsequent deletion of the diaphragms of endothelial fenestrae, which led to plasma protein extravasation, PLE, and ultimately death. Keywords: Endothelium, Fenestrae, Hypertriglyceridemia, Hypoalbuminemia, Hypoproteinemia, Very Early Onset Inflammatory Bowel Disease, Monogenic Diseases, Protein-Losing Enteropathy, Whole-Exome Sequencing

Petrus Abelardus se Megariaanse argument in Theologia 'Scholarium'

African Journals Online (AJOL)

Test

7 Jun 2011 ... Martin Heidegger se beroemde opmerking (1958:37; 'Die wêreld word donker . .... Luther en die Wes-Europese Kerkhervorming}]). 7. ...... King, P., 2004, 'Peter Abelard', Stanford Encyclopedia of Philosophy, viewed February.

A glycogene mutation map for discovery of diseases of glycosylation

DEFF Research Database (Denmark)

Hansen, Lars; Lind-Thomsen, Allan; Joshi, Hiren J

2015-01-01

homologous families. However, Genome-Wide-Association Studies (GWAS) have identified such isoenzyme genes as candidates for different diseases, but validation is not straightforward without biomarkers. Large-scale whole exome sequencing (WES) provides access to mutations in e.g. glycosyltransferase genes...... in populations, which can be used to predict and/or analyze functional deleterious mutations. Here, we constructed a draft of a Functional Mutational Map of glycogenes, GlyMAP, from WES of a rather homogenous population of 2,000 Danes. We catalogued all missense mutations and used prediction algorithms, manual...... inspection, and in case of CAZy family GT27 experimental analysis of mutations to map deleterious mutations. GlyMAP provides a first global view of the genetic stability of the glycogenome and should serve as a tool for discovery of novel CDGs....

76 FR 39245 - Energy Conservation Program: Energy Conservation Standards for Residential Furnaces and...

Science.gov (United States)

2011-07-06

... Wes.Anderson@ee.doe.gov . Mr. Eric Stas or Ms. Jennifer Tiedeman, U.S. Department of Energy, Office of.... Wesley Anderson (central air conditioners and heat pumps), U.S. Department of Energy, Office of Energy...

kardinale aspekte van nasionale diensplig met spesifieke verwysing ...

African Journals Online (AJOL)

This is the case with organizations such as the. South African ..... Federale Republiek van Wes-Duitsland: The Force Structure in the. Federal Republic of ... Defense Intelligence Agency& Arms and Armour Press, Londen1979, p 121. 8.

Fighting the Flu

Centers for Disease Control (CDC) Podcasts

2011-03-08

Wes Studi, Hollywood actor, urges Native peoples to know the facts about the flu.  Created: 3/8/2011 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 3/8/2011.

Electoral system and electoral campaign in Ancient Rome

Directory of Open Access Journals (Sweden)

Notari Tamaš

2011-01-01

Full Text Available One of the most famous orators of the Antiquity, Marcus Tullius Cicero entered the election for the consul's position held in 64 B.C. arranged under extremely disturbed circumstances and he won the consulatus for 63 B.C. Difficulties were caused among others by the fact that an indebted nobleman called Lucius Sergius Catilina saw the only breakthrough for ensuring his political and financial survival in being elected consul, and manifested that in case he would lose he would be willing to take as well violent actions (later, he actually carried out his threats. The orator's younger brother, Quintus Tullius Cicero wanted to help his brother in his campaign foreseen as having quite a lot of turns; so, he wrote a manual for him on the lawful and illegal instruments that could be used in the elections. This work, Commentariolum petitionis (A Handbook for Applicants for Offices is the first summary of campaign strategy in the history of mankind. In addition to the evaluation of the given situation, the presentation (and exploitation of the weaknesses of counter nominees, the book provides advice on several counts that might possibly continue to have relevance even today. We do not know to what extent the experienced politician, Cicero adhered to his younger brother's advice; it is, however, a fact that he was elected consul, and as a consul he defeated Catilina's revolt in. 63 B.C.

Whole-exome sequencing for mutation detection in pediatric disorders of insulin secretion: Maturity onset diabetes of the young and congenital hyperinsulinism.

Science.gov (United States)

Johnson, S R; Leo, P J; McInerney-Leo, A M; Anderson, L K; Marshall, M; McGown, I; Newell, F; Brown, M A; Conwell, L S; Harris, M; Duncan, E L

2018-06-01

To assess the utility of whole-exome sequencing (WES) for mutation detection in maturity-onset diabetes of the young (MODY) and congenital hyperinsulinism (CHI). MODY and CHI are the two commonest monogenic disorders of glucose-regulated insulin secretion in childhood, with 13 causative genes known for MODY and 10 causative genes identified for CHI. The large number of potential genes makes comprehensive screening using traditional methods expensive and time-consuming. Ten subjects with MODY and five with CHI with known mutations underwent WES using two different exome capture kits (Nimblegen SeqCap EZ Human v3.0 Exome Enrichment Kit, Nextera Rapid Capture Exome Kit). Analysis was blinded to previously identified mutations, and included assessment for large deletions. The target capture of five exome capture technologies was also analyzed using sequencing data from >2800 unrelated samples. Four of five MODY mutations were identified using Nimblegen (including a large deletion in HNF1B). Although targeted, one mutation (in INS) had insufficient coverage for detection. Eleven of eleven mutations (six MODY, five CHI) were identified using Nextera Rapid (including the previously missed mutation). On reconciliation, all mutations concorded with previous data and no additional variants in MODY genes were detected. There were marked differences in the performance of the capture technologies. WES can be useful for screening for MODY/CHI mutations, detecting both point mutations and large deletions. However, capture technologies require careful selection. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Estimation of kinship coefficient in structured and admixed populations using sparse sequencing data.

Directory of Open Access Journals (Sweden)

Jinzhuang Dou

2017-09-01

Full Text Available Knowledge of biological relatedness between samples is important for many genetic studies. In large-scale human genetic association studies, the estimated kinship is used to remove cryptic relatedness, control for family structure, and estimate trait heritability. However, estimation of kinship is challenging for sparse sequencing data, such as those from off-target regions in target sequencing studies, where genotypes are largely uncertain or missing. Existing methods often assume accurate genotypes at a large number of markers across the genome. We show that these methods, without accounting for the genotype uncertainty in sparse sequencing data, can yield a strong downward bias in kinship estimation. We develop a computationally efficient method called SEEKIN to estimate kinship for both homogeneous samples and heterogeneous samples with population structure and admixture. Our method models genotype uncertainty and leverages linkage disequilibrium through imputation. We test SEEKIN on a whole exome sequencing dataset (WES of Singapore Chinese and Malays, which involves substantial population structure and admixture. We show that SEEKIN can accurately estimate kinship coefficient and classify genetic relatedness using off-target sequencing data down sampled to ~0.15X depth. In application to the full WES dataset without down sampling, SEEKIN also outperforms existing methods by properly analyzing shallow off-target data (~0.75X. Using both simulated and real phenotypes, we further illustrate how our method improves estimation of trait heritability for WES studies.

An Analysis of FM Jamming and Noise Quality Measures

Science.gov (United States)

1993-12-01

equipment setup is shown in figure 6. For reasons of practicality and manageability , all equipment was chosen to be commercially available and of a fairly...bins based on the size of the parameter F. It computes a smoothed "Turner Noise Qaulity " similar to the noise quality measure employed by Daly in his...recý.orate for :nf-,aton Doe,A-,ým5 1o- A c-t•s. )2 15 efferso Oarts H,9gPay, Srte 1204. ArtOngton, VA 222024302 and to the Of"ce of Management and aucige

A VLSI System-on-Chip for Particle Detectors

CERN Document Server

AUTHOR|(CDS)2078019

In this thesis I present a System-on-Chip (SoC) I designed to oer a self- contained, compact data acquisition platform for micromegas detector mon- itoring. I carried on my work within the RD-51 collab oration of CERN. With a companion ADC, my architecture is capable to acquire the signal from a detector electro de, pro cess the data and p erform monitoring tests. The SoC is built around on a custom 8-bit micropro cessor with internal mem- ory resources and emb eds the p eripherals to b e interf...

Prostate Cancer: Improving the Flow of Research.

Science.gov (United States)

Lawton, Colleen A F

2018-04-01

Prostate cancer is the most common nonskin cancer diagnosed in U.S. men and kills over 27 000 men annually. Thus, improving the outcomes for patients diagnosed with this disease is imperative. There has been a considerable amount of research done over the past several decades resulting in more cures than ever, but the death rate is still unacceptable. This oration addresses the progress that we have made over the past several decades and outlines the work yet to be done, as well as some processes to make that work happen. © RSNA, 2018.

Discovery and resolve: the Human Genetics Society of Australasia Oration 2011.

Science.gov (United States)

Pearn, John

2011-10-01

Human genetics spans every facet of biology from molecular science, through laboratory and clinical practice, to psychology and anthropology. In each of these areas, the history of human genetics has been punctuated by paradigm shifts in knowledge. Each such new concept has been received with skepticism, often with perplexity, and sometimes with frank incredulity. Such comprise the datum milestones along the path leading to our present corpus of genetic knowledge. In parallel to the personal threats to Copernicus and Galileo in the field of astronomy in the 17th century, almost all genetic discoveries of the 19th and 20th centuries were seen as challenges to the received wisdom, and sometimes the social order, of their time and place. Researchers, scientists and clinicians encountering such new and often-heretical paradigm shifts have required considerable resolve to promote and publish their work. Just as in the field of astronomy, new directions in genetics have threatened not only the reputations and sometimes the careers of scientists, but also have been challenges to fundamental religious and sociological beliefs in society more broadly. Examples followed the discovery of biological sexual dimorphism (in plants as well as animals) by Nehemiah Grew (1641-1712). Darwinian evolution, Mendel's First and Second Laws, the existence of mitochondrial genes, apoptosis and its genetic basis, and uniparental disomy are more recent examples. Many of these new revelations, which today have led to the current understanding of fundamental biology, were discovered by individuals working in relative isolation. To promote and publish findings that fundamentally challenge received wisdom continues to require considerable resolve, if not courage. Herein lies a message for all clinicians and researchers.

75 FR 56578 - Renewal of the Advisory Committee on Apprenticeship (ACA), and an Open Meeting

Science.gov (United States)

2010-09-16

..., Training Project Manager, Corporate Training Development, United Parcel Service, Atlanta, Georgia. Mr. Wes... Training, United Association of Journeymen & Apprentices of the Plumbing & Pipe Fitting Industry of the U.S... America, Pomfret Center, Connecticut. Ms. Charissa Raynor, Executive Director, Service Employees...

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing

NARCIS (Netherlands)

I. Jansen (Iris); Ye, H. (Hui); Heetveld, S. (Sasja); Lechler, M.C. (Marie C.); Michels, H. (Helen); Seinstra, R.I. (Renée I.); Lubbe, S.J. (Steven J.); Drouet, V. (Valérie); S. Lesage (Suzanne); E. Majounie (Elisa); Gibbs, J.R. (J.Raphael); M.A. Nalls (Michael); M. Ryten (Mina); Botia, J.A. (Juan A.); J. Vandrovcova (Jana); J. Simón-Sánchez (Javier); Castillo-Lizardo, M. (Melissa); P. Rizzu (Patrizia); Blauwendraat, C. (Cornelis); Chouhan, A.K. (Amit K.); Li, Y. (Yarong); Yogi, P. (Puja); N. Amin (Najaf); C.M. van Duijn (Cornelia); Morris, H.R. (Huw R.); Brice, A. (Alexis); A. Singleton (Andrew); David, D.C. (Della C.); Nollen, E.A. (Ellen A.); A. Jain (Ashok); J.M. Shulman; P. Heutink (Peter); D.G. Hernandez (Dena); S. Arepalli (Sampath); J. Brooks (Janet); Price, R. (Ryan); Nicolas, A. (Aude); S. Chong (Sean); M.R. Cookson (Mark); A. Dillman (Allissa); M. Moore (Matt); B.J. Traynor (Bryan); A. Singleton (Andrew); V. Plagnol (Vincent); Nicholas W Wood,; U.-M. Sheerin (Una-Marie); Jose M Bras,; K. Charlesworth (Kate); M. Gardner (Mac); R. Guerreiro (Rita); D. Trabzuni (Danyah); Hardy, J. (John); M. Sharma; M. Saad (Mohamad); Javier Simón-Sánchez,; C. Schulte (Claudia); J.C. Corvol (Jean-Christophe); Dürr, A. (Alexandra); M. Vidailhet (M.); S. Sveinbjörnsdóttir (Sigurlaug); R.A. Barker (Roger); Caroline H Williams-Gray,; Y. Ben-Shlomo; H.W. Berendse (Henk W.); K.D. van Dijk (Karin); D. Berg (Daniela); K. Brockmann; K.D. Wurster (Kathrin); Mätzler, W. (Walter); Gasser, T. (Thomas); M. Martinez (Maria); R.M.A. de Bie (Rob); A. Biffi (Alessandro); D. Velseboer (Daan); B.R. Bloem (Bastiaan); B. Post (Bart); M. Wickremaratchi (Mirdhu); B. van de Warrenburg (Bart); Z. Bochdanovits (Zoltan); M. von Bonin (Malte); H. Pétursson (Hjörvar); O. Riess (Olaf); D.J. Burn (David); Lubbe, S. (Steven); Cooper, J.M. (J Mark); N.H. McNeill (Nathan); Schapira, A. (Anthony); Lungu, C. (Codrin); Chen, H. (Honglei); Dong, J. (Jing); Chinnery, P.F. (Patrick F.); G. Hudson (Gavin); Clarke, C.E. (Carl E.); C. Moorby (Catriona); C. Counsell (Carl); P. Damier (Philippe); J.-F. Dartigues; P. Deloukas (Panagiotis); E. Gray (Emma); T. Edkins (Ted); Hunt, S.E. (Sarah E.); S.C. Potter (Simon); A. Tashakkori-Ghanbaria (Avazeh); G. Deuschl (Günther); D. Lorenz (Delia); D.T. Dexter (David); F. Durif (Frank); J. Evans (Jonathan Mark); Langford, C. (Cordelia); T. Foltynie (Thomas); A.M. Goate (Alison); C. Harris (Clare); J.J. van Hilten (Jacobus); A. Hofman (Albert); J.R. Hollenbeck (John R.); J.L. Holton (Janice); Hu, M. (Michele); X. Huang (Xiaohong); Illig, T. (Thomas); P.V. Jónsson (Pálmi); J.-C. Lambert; S.S. O'Sullivan (Sean); T. Revesz (Tamas); K. Shaw (Karen); A.J. Lees (Andrew); P. Lichtner (Peter); P. Limousin (Patricia); G. Lopez; Escott-Price, V. (Valentina); J. Pearson (Justin); N. Williams (Nigel); E. Mudanohwo (Ese); J.S. Perlmutter (Joel); Pollak, P. (Pierre); F. Rivadeneira Ramirez (Fernando); A.G. Uitterlinden (André); S.J. Sawcer (Stephen); H. Scheffer (Hans); I. Shoulson (Ira); L. Shulman (Lee); Smith, C. (Colin); R. Walker (Robert); C.C.A. Spencer (Chris C.); A. Strange (Amy); H. Stefansson (Hreinn); F. Bettella (Francesco); J-A. Zwart (John-Anker); Stockton, J.D. (Joanna D.); D. Talbot; C.M. Tanner (Carlie); F. Tison (François); S. Winder-Rhodes (Sophie); K.P. Bhatia (Kailash)

2017-01-01

textabstractBackground: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we

TECRL, a new life-threatening inherited arrhythmia gene associated with overlapping clinical features of both LQTS and CPVT

NARCIS (Netherlands)

Devalla, Harsha D.; Gélinas, Roselle; Aburawi, Elhadi H.; Beqqali, Abdelaziz; Goyette, Philippe; Freund, Christian; Chaix, Marie-A.; Tadros, Rafik; Jiang, Hui; Le Béchec, Antony; Monshouwer-Kloots, Jantine J.; Zwetsloot, Tom; Kosmidis, Georgios; Latour, Frédéric; Alikashani, Azadeh; Hoekstra, Maaike; Schlaepfer, Jurg; Mummery, Christine L.; Stevenson, Brian; Kutalik, Zoltan; de Vries, Antoine Af; Rivard, Léna; Wilde, Arthur Am; Talajic, Mario; Verkerk, Arie O.; Al-Gazali, Lihadh; Rioux, John D.; Bhuiyan, Zahurul A.; Passier, Robert

2016-01-01

Genetic causes of many familial arrhythmia syndromes remain elusive. In this study, whole-exome sequencing (WES) was carried out on patients from three different families that presented with life-threatening arrhythmias and high risk of sudden cardiac death (SCD). Two French Canadian probands

Our Cultures Are Our Source of Health

Centers for Disease Control (CDC) Podcasts

2013-03-04

Wes Studi, Hollywood actor, highlights the wisdom of cultural knowledge to promote health and prevent type 2 diabetes.  Created: 3/4/2013 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 3/4/2013.

Verhoudingsbemarking by reisagentskappe in die Wes-Kaap Provinsie / Mornay Roberts-Lombard

OpenAIRE

Roberts-Lombard, Mornay

2006-01-01

Relationship marketing has received much attention and widespread publicity over the past ten years and has moved to the forefront of research and practice. It provides companies with a management tool to establish economically profitable relationships, networks and interactions with different, but equally important stakeholder markets. The marketing concept as reflected in the four P's of the marketing mix was prominent in marketing practice and thinking until the mid-1980s, w...

Design of the WES Centrifuge (Phase 3A and 3B)

Science.gov (United States)

1993-03-31

the facility; heme ANS&A’a role was to encourage users from different laboratories by discussing the opportunities that presented themselves on the...the ability to interpret users’ needs and for conceptual model defintion , den aquisition and mastrking. Possible arrangements whereby RP could spend...equipment was discussed. CRREL involvement would be needed in the defintion of initial experiments and in the devdlopme of a programme for the commismoning

Clinical exome sequencing reports: current informatics practice and future opportunities.

Science.gov (United States)

Swaminathan, Rajeswari; Huang, Yungui; Astbury, Caroline; Fitzgerald-Butt, Sara; Miller, Katherine; Cole, Justin; Bartlett, Christopher; Lin, Simon

2017-11-01

The increased adoption of clinical whole exome sequencing (WES) has improved the diagnostic yield for patients with complex genetic conditions. However, the informatics practice for handling information contained in whole exome reports is still in its infancy, as evidenced by the lack of a common vocabulary within clinical sequencing reports generated across genetic laboratories. Genetic testing results are mostly transmitted using portable document format, which can make secondary analysis and data extraction challenging. This paper reviews a sample of clinical exome reports generated by Clinical Laboratory Improvement Amendments-certified genetic testing laboratories at tertiary-care facilities to assess and identify common data elements. Like structured radiology reports, which enable faster information retrieval and reuse, structuring genetic information within clinical WES reports would help facilitate integration of genetic information into electronic health records and enable retrospective research on the clinical utility of WES. We identify elements listed as mandatory according to practice guidelines but are currently missing from some of the clinical reports, which might help to organize the data when stored within structured databases. We also highlight elements, such as patient consent, that, although they do not appear within any of the current reports, may help in interpreting some of the information within the reports. Integrating genetic and clinical information would assist the adoption of personalized medicine for improved patient care and outcomes. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Whole Exome Sequencing for the differential diagnosis of primary adrenal insufficiency in children

Directory of Open Access Journals (Sweden)

Li F Chan

2015-08-01

Full Text Available Adrenal insufficiency is a rare, but potentially fatal medical condition. In children the cause is most commonly congenital and in recent years a growing number of causative gene mutations have been identified resulting in a myriad of syndromes that share adrenal insufficiency as one of the main characteristics. The evolution of adrenal insufficiency is dependent on the variant and the particular gene affected, meaning rapid and accurate diagnosis is imperative for effective treatment of the patient. Common practice is for candidate genes to be sequenced individually, which is a time consuming process and complicated by overlapping clinical phenotypes. However, with the availability, and increasing cost effectiveness of whole exome sequencing there is the potential for this to become a powerful diagnostic tool. Here we report the results of whole exome sequencing of 43 patients referred to us with a diagnosis of familial glucocorticoid deficiency (FGD who were mutation negative for MC2R, MRAP and STAR the most commonly mutated genes in FGD. WES provided a rapid genetic diagnosis in 17/43 sequenced patients, for the remaining 60% the gene defect may be within intronic/regulatory regions not covered by WES or may be in gene(s representing novel aetiologies. The diagnosis of isolated or familial glucocorticoid deficiency was only confirmed in 3 of the 17 patients, other genetic diagnoses were adrenal hypo- and hyperplasia, Triple A and autoimmune polyendocrinopathy syndrome type I, emphasizing both the difficulty of phenotypically distinguishing between disorders of PAI and the utility of WES as a tool to achieve this.

Whole Exome Sequencing for a Patient with Rubinstein-Taybi Syndrome Reveals de Novo Variants besides an Overt CREBBP Mutation

Directory of Open Access Journals (Sweden)

Hee Jeong Yoo

2015-03-01

Full Text Available Rubinstein-Taybi syndrome (RSTS is a rare condition with a prevalence of 1 in 125,000–720,000 births and characterized by clinical features that include facial, dental, and limb dysmorphology and growth retardation. Most cases of RSTS occur sporadically and are caused by de novo mutations. Cytogenetic or molecular abnormalities are detected in only 55% of RSTS cases. Previous genetic studies have yielded inconsistent results due to the variety of methods used for genetic analysis. The purpose of this study was to use whole exome sequencing (WES to evaluate the genetic causes of RSTS in a young girl presenting with an Autism phenotype. We used the Autism diagnostic observation schedule (ADOS and Autism diagnostic interview revised (ADI-R to confirm her diagnosis of Autism. In addition, various questionnaires were used to evaluate other psychiatric features. We used WES to analyze the DNA sequences of the patient and her parents and to search for de novo variants. The patient showed all the typical features of Autism, WES revealed a de novo frameshift mutation in CREBBP and de novo sequence variants in TNC and IGFALS genes. Mutations in the CREBBP gene have been extensively reported in RSTS patients, while potential missense mutations in TNC and IGFALS genes have not previously been associated with RSTS. The TNC and IGFALS genes are involved in central nervous system development and growth. It is possible for patients with RSTS to have additional de novo variants that could account for previously unexplained phenotypes.

Herklots 1857

African Journals Online (AJOL)

STORAGESEVER

2009-04-20

Apr 20, 2009 ... the Lagos metropolitan area (WES, 1997) and their ... environmental control settings of crude oil spillages in ... impact and risk assessment now facing ecotoxicologists .... produced the biological response (LC50 or median response levels ..... mixtures of heavy metals against the mangrove periwinkle.

Tumour burden in early stage Hodgkin's disease: the single most important prognostic factor for outcome after radiotherapy

DEFF Research Database (Denmark)

Specht, L; Nordentoft, A M; Cold, Søren

1987-01-01

One hundred and forty-two patients with Hodgkin's disease PS I or II were treated with total or subtotal nodal irradiation as part of a prospective randomized trial in the Danish National Hodgkin Study during the period 1971-83. They were followed till death or--at the time of this analysis......--from 15 to 146 months after initiation of therapy. The initial tumour burden of each patient was assessed, combining tumour size of each involved region and number of regions involved. Tumour burden thus assessed proved to be the single most important prognostic factor with regard to disease free survival...

The Language of Conflict in Northern Ireland: Gerry Adams vs. Ian Paisley

Directory of Open Access Journals (Sweden)

Kim Grego

2010-03-01

    The discourse analysis of the texts collected is supported by computer-aided analysis. Two aspects are being focussed on, in particular: 1 the use of same/different linguistic resources by the same orators to discuss same/different subjects over the years; and 2 the overall influence of language on politics, i.e. how words are used to exercise power.     It is hoped that the present study may help clarify aspects of the evolution of political discourse in Northern Ireland, in general, and of the argumentative skills and strategies of the above two politicians, in particular.

Is it true that our target groups are out of reach?

Directory of Open Access Journals (Sweden)

Dušana Findeisen

1999-12-01

Full Text Available In article Dušana Findeisen examines the question of permanent and planned collaboration with the media. Such collaboration is to be established between the media and educational organisations or different project groups. Thus, it seems that this collab­ oration is of outmost importance for those project groups or non-governmental organisations or educational organisations striving for changes in the social environment and for the benifit of groups of the socially excluded. Moreover, Dušana Findeisen gives particular attention to the question of school out-drops and how to reach them.

Our Cultures Are Our Source of Health PSA (:60)

Centers for Disease Control (CDC) Podcasts

2013-03-04

In this 60 second Public Service Announcement, Wes Studi, Hollywood actor, highlights the wisdom of cultural knowledge to promote health and prevent type 2 diabetes.  Created: 3/4/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 3/4/2013.

Our Cultures Are Our Source of Health PSA (:30)

Centers for Disease Control (CDC) Podcasts

2013-03-04

In this 30 second Public Service Announcement, Wes Studi, Hollywood actor, highlights the wisdom of cultural knowledge to promote health and prevent type 2 diabetes.  Created: 3/4/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 3/4/2013.

Rimeigi rimeigi rimeik / Alar Niineväli

Index Scriptorium Estoniae

Niineväli, Alar

2009-01-01

USA 2009.a. õudusfilmist "Viimane maja vasakul" ("The Last House on the Left"), režissöör Dennis Iliadis. Filmi on vaadatud kui uusversiooni Wes Craveni samanimelisest 1972.a. filmist, mis omakorda on lähtunud Ingmar Bergmani 1960.a. filmist "Neitsiallikas" ("Jungfrukällan")

Importance of Skin Changes in the Differential Diagnosis of Congenital Muscular Dystrophies

Directory of Open Access Journals (Sweden)

Uluç Yis

2016-01-01

Full Text Available Megaconial congenital muscular dystrophy (OMIM 602541 is characterized with early-onset hypotonia, muscle wasting, proximal weakness, cardiomyopathy, mildly elevated serum creatine kinase (CK levels, and mild-to-moderate intellectual disability. We report two siblings in a consanguineous family admitted for psychomotor delay. Physical examination revealed proximal muscle weakness, contractures in the knee of elder sibling, diffuse mild generalized muscle atrophy, and dry skin with ichthyosis together with multiple nummular eczema in both siblings. Serum CK values were elevated up to 500 U/L. For genetic work-up, we performed whole exome sequencing (WES after Nimblegen enrichment on the Illumina platform. The WES revealed a novel homozygous missense mutation in the Choline Kinase-Beta (CHKB gene c.1031G>A (p.R344Q in exon 9. Ichthyosis-like skin changes with intense pruritus and nummular eczema may lead to clinical diagnosis in cases with megaconial congenital muscular dystrophy.

Perceived nursing work environment of acute care pediatric nurses.

Science.gov (United States)

Kotzer, Anne Marie; Koepping, Dianne M; LeDuc, Karen

2006-01-01

Nurse job satisfaction is a complex phenomenon and includes elements of the work environment. The purpose of this study was to evaluate nurses' perception of their real (current) and ideal (preferred) work environment in a pediatric tertiary care setting. Using a descriptive survey design, a convenience sample of staff nurses from three inpatient units was surveyed using the Work Environment Scale (WES) by Moos (1994). The WES consists of 10 subscales characterizing three dimensions: Relationship, Personal Growth, and System Maintenance and Change. Overall, nurses affirmed a highly positive and supportive work environment on their units. Non-significant findings between the real and ideal scores for the Involvement and Managerial Control subscales suggest that staff are concerned about and committed to their work, and satisfied with their managers' use of rules and procedures. Statistically significant differences between selected real and ideal subscale scores will help target intervention strategies to enhance the nursing work environment.

Early-Onset Severe Encephalopathy with Epilepsy: The BRAT1 Gene Should Be Added to the List of Causes.

Science.gov (United States)

van de Pol, Laura A; Wolf, Nicole I; van Weissenbruch, Mirjam M; Stam, Cornelie J; Weiss, Janneke M; Waisfisz, Quinten; Kevelam, Sietske H; Bugiani, Mariana; van de Kamp, Jiddeke M; van der Knaap, Marjo S

2015-12-01

A variety of pathologies can underlie early-onset severe encephalopathy with epilepsy. To aid the diagnostic process in such patients we present an overview of causes, including the rapidly expanding list of genes involved. When no explanation is found, whole-exome sequencing (WES) can be used in an attempt to identify gene defects in patients suspected to suffer from a genetic form. We describe three siblings, born to consanguineous parents, with a lethal severe epileptic encephalopathy with early-infantile onset, including their magnetic resonance imaging, electroencephalography and, in one case, neuropathological findings. Using WES a homozygous frameshift mutation in the BRAT1 gene, c.638dup p.(Val214Glyfs*189), was identified. We present our cases in the context of all published cases with mutations in the BRAT1 gene and conclude that BRAT1 should be added to the growing list of genes related to early-onset severe encephalopathy with epilepsy. Georg Thieme Verlag KG Stuttgart · New York.

Qualitative case studies of professional-level workers with traumatic brain injuries: A contextual approach to job accommodation and retention.

Science.gov (United States)

Roessler, Richard T; Rumrill, Phillip D; Rumrill, Stuart P; Minton, Deborah L; Hendricks, Deborah J; Sampson, Elaine; Stauffer, Callista; Scherer, Marcia J; Nardone, Amanda; Leopold, Anne; Jacobs, Karen; Elias, Eileen

2017-09-14

Traumatic brain injury (TBI) is a multi-systemic disability that causes a wide range of difficulties with personal and social functioning. Four individuals with TBI participated in an evaluation of barriers to their continued employment following graduation from college. A trained interviewer completed the Work Experience Survey (WES) in teleconsultation sessions with each participant. Researchers applied a qualitative case study research design. Participants reported a wide range of difficulties in performing essential functions of their jobs (3 to 24) that have the potential to significantly affect their productivity. Career mastery problems reflected outcomes associated with TBI such as 'believing that others think I do a good job' and 'having the resources (e.g., knowledge, tools, supplies, and equipment) needed to do the job.' Indicative of their wish to continue their current employment, participants reported high levels of job satisfaction. The WES is a cost-effective needs assessment tool to aid health and rehabilitation professionals in providing on-the-job supports to workers with TBI.

Perceived levels of burnout of Veterans Administration therapeutic recreation personnel.

Science.gov (United States)

Wade-Campbell, K N; Anderson, S C

1987-01-01

This study investigated the relationship between work-related variables and perceived levels of burnout of therapeutic recreation personnel who work with long-term psychiatric patients in Veterans Administration hospitals. Subjects completed a three-part instrument composed of a demographic questionnaire, the Maslach Burnout Inventory and the Work Environment Scale. Of the 511 subjects surveyed, 287 (56%) responded with usable questionnaires. The demographic, job- and profession-related variables were found to be significantly related to burnout. The eta values were somewhat low. The WES variables accounted for 20.9% of the variance in the burnout measures. The WES variables accounted for 20.9% of the variance in the burnout measures. The most salient relationships emerged between the emotional exhaustion and the depersonalization subscales and clarity, supervisor support, involvement, work pressure, autonomy, innovation, peer cohesion, task orientation and physical comfort. In comparison with other groups of human service professionals, therapeutic recreation personnel experienced low levels of emotional exhaustion, moderate levels of depersonalization, and somewhat lower levels of personal accomplishment.

Syndromic intellectual disability: a new phenotype caused by an aromatic amino acid decarboxylase gene (DDC) variant.

Science.gov (United States)

Graziano, Claudio; Wischmeijer, Anita; Pippucci, Tommaso; Fusco, Carlo; Diquigiovanni, Chiara; Nõukas, Margit; Sauk, Martin; Kurg, Ants; Rivieri, Francesca; Blau, Nenad; Hoffmann, Georg F; Chaubey, Alka; Schwartz, Charles E; Romeo, Giovanni; Bonora, Elena; Garavelli, Livia; Seri, Marco

2015-04-01

The causative variant in a consanguineous family in which the three patients (two siblings and a cousin) presented with intellectual disability, Marfanoid habitus, craniofacial dysmorphisms, chronic diarrhea and progressive kyphoscoliosis, has been identified through whole exome sequencing (WES) analysis. WES study identified a homozygous DDC variant in the patients, c.1123C>T, resulting in p.Arg375Cys missense substitution. Mutations in DDC cause a recessive metabolic disorder (aromatic amino acid decarboxylase, AADC, deficiency, OMIM #608643) characterized by hypotonia, oculogyric crises, excessive sweating, temperature instability, dystonia, severe neurologic dysfunction in infancy, and specific abnormalities of neurotransmitters and their metabolites in the cerebrospinal fluid (CSF). In our family, analysis of neurotransmitters and their metabolites in patient's CSF shows a pattern compatible with AADC deficiency, although the clinical signs are different from the classic form. Our work expands the phenotypic spectrum associated with DDC variants, which therefore can cause an additional novel syndrome without typical movement abnormalities. Copyright © 2015 Elsevier B.V. All rights reserved.

Abiotic and Biotic Mechanisms Controlling In Situ Remediation of NDMA

Science.gov (United States)

2009-05-01

1985; Mitch et al. 2003) and soil microcosms ( Mallik and Testai 1981). These results were confirmed in our laboratory (WES) using 14C-NDMA (Figure...9- Fluorenylmethylchloroformate.” Journal of Chromatography 721(2):231–239. Mallik MA and K Testai. 1981. “Transformation of Nitrosamines in Soil

Early-Onset Severe Encephalopathy with Epilepsy: The BRAT1 Gene Should Be Added to the List of Causes

NARCIS (Netherlands)

van de Pol, L.A.; Wolf, N.I.; van Weissenbruch, M.M.; Stam, C.J.; Weiss, M.M.; Waisfisz, Q.; Kevelam, S.H.; Bugiani, M.; van de Kamp, J.M.; Knaap, M.

2015-01-01

A variety of pathologies can underlie early-onset severe encephalopathy with epilepsy. To aid the diagnostic process in such patients we present an overview of causes, including the rapidly expanding list of genes involved. When no explanation is found, whole-exome sequencing (WES) can be used in an

Importance of comprehensive molecular profiling for clinical outcome in children with recurrent cancer

DEFF Research Database (Denmark)

Østrup, Olga; Nysom, Karsten; Scheie, David

2018-01-01

treatment. Results: Of the 48 patients, 33 had actionable findings. The most efficient method for the identification of actionable findings was WES (39%), followed by SNP array (37%). Of note, gene fusions were identified by RNAseq in 21% of the samples. Eleven findings led to clinical intervention, i...

The Use of Non-Variant Sites to Improve the Clinical Assessment of Whole-Genome Sequence Data.

Directory of Open Access Journals (Sweden)

Alberto Ferrarini

Full Text Available Genetic testing, which is now a routine part of clinical practice and disease management protocols, is often based on the assessment of small panels of variants or genes. On the other hand, continuous improvements in the speed and per-base costs of sequencing have now made whole exome sequencing (WES and whole genome sequencing (WGS viable strategies for targeted or complete genetic analysis, respectively. Standard WGS/WES data analytical workflows generally rely on calling of sequence variants respect to the reference genome sequence. However, the reference genome sequence contains a large number of sites represented by rare alleles, by known pathogenic alleles and by alleles strongly associated to disease by GWAS. It's thus critical, for clinical applications of WGS and WES, to interpret whether non-variant sites are homozygous for the reference allele or if the corresponding genotype cannot be reliably called. Here we show that an alternative analytical approach based on the analysis of both variant and non-variant sites from WGS data allows to genotype more than 92% of sites corresponding to known SNPs compared to 6% genotyped by standard variant analysis. These include homozygous reference sites of clinical interest, thus leading to a broad and comprehensive characterization of variation necessary to an accurate evaluation of disease risk. Altogether, our findings indicate that characterization of both variant and non-variant clinically informative sites in the genome is necessary to allow an accurate clinical assessment of a personal genome. Finally, we propose a highly efficient extended VCF (eVCF file format which allows to store genotype calls for sites of clinical interest while remaining compatible with current variant interpretation software.

Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders.

Science.gov (United States)

Codina-Solà, Marta; Rodríguez-Santiago, Benjamín; Homs, Aïda; Santoyo, Javier; Rigau, Maria; Aznar-Laín, Gemma; Del Campo, Miguel; Gener, Blanca; Gabau, Elisabeth; Botella, María Pilar; Gutiérrez-Arumí, Armand; Antiñolo, Guillermo; Pérez-Jurado, Luis Alberto; Cuscó, Ivon

2015-01-01

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders with high heritability. Recent findings support a highly heterogeneous and complex genetic etiology including rare de novo and inherited mutations or chromosomal rearrangements as well as double or multiple hits. We performed whole-exome sequencing (WES) and blood cell transcriptome by RNAseq in a subset of male patients with idiopathic ASD (n = 36) in order to identify causative genes, transcriptomic alterations, and susceptibility variants. We detected likely monogenic causes in seven cases: five de novo (SCN2A, MED13L, KCNV1, CUL3, and PTEN) and two inherited X-linked variants (MAOA and CDKL5). Transcriptomic analyses allowed the identification of intronic causative mutations missed by the usual filtering of WES and revealed functional consequences of some rare mutations. These included aberrant transcripts (PTEN, POLR3C), deregulated expression in 1.7% of mutated genes (that is, SEMA6B, MECP2, ANK3, CREBBP), allele-specific expression (FUS, MTOR, TAF1C), and non-sense-mediated decay (RIT1, ALG9). The analysis of rare inherited variants showed enrichment in relevant pathways such as the PI3K-Akt signaling and the axon guidance. Integrative analysis of WES and blood RNAseq data has proven to be an efficient strategy to identify likely monogenic forms of ASD (19% in our cohort), as well as additional rare inherited mutations that can contribute to ASD risk in a multifactorial manner. Blood transcriptomic data, besides validating 88% of expressed variants, allowed the identification of missed intronic mutations and revealed functional correlations of genetic variants, including changes in splicing, expression levels, and allelic expression.

Panel-based whole exome sequencing identifies novel mutations in microphthalmia and anophthalmia patients showing complex Mendelian inheritance patterns.

Science.gov (United States)

Riera, Marina; Wert, Ana; Nieto, Isabel; Pomares, Esther

2017-11-01

Microphthalmia and anophthalmia (MA) are congenital eye abnormalities that show an extremely high clinical and genetic complexity. In this study, we evaluated the implementation of whole exome sequencing (WES) for the genetic analysis of MA patients. This approach was used to investigate three unrelated families in which previous single-gene analyses failed to identify the molecular cause. A total of 47 genes previously associated with nonsyndromic MA were included in our panel. WES was performed in one affected patient from each family using the AmpliSeq TM Exome technology and the Ion Proton TM platform. A novel heterozygous OTX2 missense mutation was identified in a patient showing bilateral anophthalmia who inherited the variant from a parent who was a carrier, but showed no sign of the condition. We also describe a new PAX6 missense variant in an autosomal-dominant pedigree affected by mild bilateral microphthalmia showing high intrafamiliar variability, with germline mosaicism determined to be the most plausible molecular cause of the disease. Finally, a heterozygous missense mutation in RBP4 was found to be responsible in an isolated case of bilateral complex microphthalmia. This study highlights that panel-based WES is a reliable and effective strategy for the genetic diagnosis of MA. Furthermore, using this technique, the mutational spectrum of these diseases was broadened, with novel variants identified in each of the OTX2, PAX6, and RBP4 genes. Moreover, we report new cases of reduced penetrance, mosaicism, and variable phenotypic expressivity associated with MA, further demonstrating the heterogeneity of such disorders. © 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Whole-Exome Sequencing in Searching for New Variants Associated With the Development of Parkinson’s Disease

Directory of Open Access Journals (Sweden)

Marina V. Shulskaya

2018-05-01

Full Text Available Background: Parkinson’s disease (PD is a complex disease with its monogenic forms accounting for less than 10% of all cases. Whole-exome sequencing (WES technology has been used successfully to find mutations in large families. However, because of the late onset of the disease, only small families and unrelated patients are usually available. WES conducted in such cases yields in a large number of candidate variants. There are currently a number of imperfect software tools that allow the pathogenicity of variants to be evaluated.Objectives: We analyzed 48 unrelated patients with an alleged autosomal dominant familial form of PD using WES and developed a strategy for selecting potential pathogenetically significant variants using almost all available bioinformatics resources for the analysis of exonic areas.Methods: DNA sequencing of 48 patients with excluded frequent mutations was performed using an Illumina HiSeq 2500 platform. The possible pathogenetic significance of identified variants and their involvement in the pathogenesis of PD was assessed using SNP and Variation Suite (SVS, Combined Annotation Dependent Depletion (CADD and Rare Exome Variant Ensemble Learner (REVEL software. Functional evaluation was performed using the Pathway Studio database.Results: A significant reduction in the search range from 7082 to 25 variants in 23 genes associated with PD or neuronal function was achieved. Eight (FXN, MFN2, MYOC, NPC1, PSEN1, RET, SCN3A and SPG7 were the most significant.Conclusions: The multistep approach developed made it possible to conduct an effective search for potential pathogenetically significant variants, presumably involved in the pathogenesis of PD. The data obtained need to be further verified experimentally.

A pilot study on the effects of a team building process on the perception of work environment in an integrative hospital for neurological rehabilitation.

Science.gov (United States)

Ostermann, Thomas; Bertram, Mathias; Büssing, Arndt

2010-03-09

Neurological rehabilitation is one of the most care-intensive challenges in the health care system requiring specialist therapeutic and nursing knowledge. In this descriptive pilot study, we investigated the effects of a team building process on perceived work environment, self-ascribed professional competence, life satisfaction, and client satisfaction in an anthroposophic specialized hospital for neurological rehabilitation. The team-building process consisted of didactic instruction and training in problem-solving, teambuilding and constructive conflict resolution. Seventy seven staff members and 44 patients' relatives were asked to complete a survey that included the Work Environment Scale (WES-10), a Life Satisfaction Scale (BMLSS), the Conviction of Therapeutic Competency (CTC) scale and the Client Satisfaction Questionnaire (CSQ-8). To evaluate the outcome of the team building process, we analyzed changes over time in the WES-10 subscales. Additionally the interrelationship between the WES-10 subscales with other subscales and with sociodemographic parameters like age, gender was calculated by means of a bivariate correlation analysis. The team building process had a significant positive effect on perceived work environment in only one area. There was a significant improvement in the ward staffs' perception of their ability to constructively resolve conflicts 3 years after inception of the team building process than there was before inception. However, even in a unit that utilized holistic treatment and nursing in the care of severely disable patients, such care necessitating a very heavy workload, the measurements on the Self Realization, Life Satisfaction and Conviction of Therapeutic Competency scales remained high and unchanged over the three year time period of the study. Strategic interventions might be an option to improve interpersonal relationships and finally quality of patient care.

Application of whole-exome sequencing to unravel the molecular basis of undiagnosed syndromic congenital neutropenia with intellectual disability.

Science.gov (United States)

Gauthier-Vasserot, Alexandra; Thauvin-Robinet, Christel; Bruel, Ange-Line; Duffourd, Yannis; St-Onge, Judith; Jouan, Thibaud; Rivière, Jean-Baptiste; Heron, Delphine; Donadieu, Jean; Bellanné-Chantelot, Christine; Briandet, Claire; Huet, Frédéric; Kuentz, Paul; Lehalle, Daphné; Duplomb-Jego, Laurence; Gautier, Elodie; Maystadt, Isabelle; Pinson, Lucile; Amram, Daniel; El Chehadeh, Salima; Melki, Judith; Julia, Sophia; Faivre, Laurence; Thevenon, Julien

2017-01-01

Neutropenia can be qualified as congenital when of neonatal onset or when associated with extra-hematopoietic manifestations. Overall, 30% of patients with congenital neutropenia (CN) remain without a molecular diagnosis after a multidisciplinary consultation and tedious diagnostic strategy. In the rare situations when neutropenia is identified and associated with intellectual disability (ID), there are few diagnostic hypotheses to test. This retrospective multicenter study reports on a clinically heterogeneous cohort of 10 unrelated patients with CN associated with ID and no molecular diagnosis prior to whole-exome sequencing (WES). WES provided a diagnostic yield of 40% (4/10). The results suggested that in many cases neutropenia and syndromic manifestations could not be assigned to the same molecular alteration. Three sub-groups of patients were highlighted: (i) severe, symptomatic chronic neutropenia, detected early in life, and related to a known mutation in the CN spectrum (ELANE); (ii) mild to moderate benign intermittent neutropenia, detected later, and associated with mutations in genes implicated in neurodevelopmental disorders (CHD2, HUWE1); and (iii) moderate to severe intermittent neutropenia as a probably undiagnosed feature of a newly reported syndrome (KAT6A). Unlike KAT6A, which seems to be associated with a syndromic form of CN, the other reported mutations may not explain the entire clinical picture. Although targeted gene sequencing can be discussed for the primary diagnosis of severe CN, we suggest that performing WES for the diagnosis of disorders associating CN with ID will not only provide the etiological diagnosis but will also pave the way towards personalized care and follow-up. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Digenic Inheritance of PROKR2 and WDR11 Mutations in Pituitary Stalk Interruption Syndrome.

Science.gov (United States)

McCormack, Shana E; Li, Dong; Kim, Yeon Joo; Lee, Ji Young; Kim, Soo-Hyun; Rapaport, Robert; Levine, Michael A

2017-07-01

Pituitary stalk interruption syndrome (PSIS, ORPHA95496) is a congenital defect of the pituitary gland characterized by the triad of a very thin/interrupted pituitary stalk, an ectopic (or absent) posterior pituitary gland, and hypoplasia or aplasia of the anterior pituitary gland. Complex genetic patterns of inheritance of this disorder are increasingly recognized. The objective of this study was to identify a genetic cause of PSIS in an affected child. Whole exome sequencing (WES) was performed by using standard techniques, with prioritized genetic variants confirmed via Sanger sequencing. To investigate the effects of one candidate variant on mutant WDR11 function, Western blotting and coimmunofluorescence were used to assess binding capacity, and leptomycin B exposure along with immunofluorescence was used to assess nuclear localization. We describe a child who presented in infancy with combined pituitary hormone deficiencies and whose brain imaging demonstrated a small anterior pituitary, ectopic posterior pituitary, and a thin, interrupted stalk. WES demonstrated heterozygous missense mutations in two genes required for pituitary development, a known loss-of-function mutation in PROKR2 (c.253C>T;p.R85C) inherited from an unaffected mother, and a WDR11 (c.1306A>G;p.I436V) mutation inherited from an unaffected father. Mutant WDR11 loses its capacity to bind to its functional partner, EMX1, and to localize to the nucleus. WES in a child with PSIS and his unaffected family implicates a digenic mechanism of inheritance. In cases of hypopituitarism in which there is incomplete segregation of a monogenic genotype with the phenotype, the possibility that a second genetic locus is involved should be considered. Copyright © 2017 Endocrine Society

2000 RSNA annual oration in diagnostic radiology: The future of interventional radiology.

Science.gov (United States)

Becker, G J

2001-08-01

Origins in imaging, procedural emphasis, and dependence on innovation characterize interventional radiology, which will continue as the field of image-guided minimally invasive therapies. A steady supply of innovators will be needed. Current workforce shortages demand that this problem be addressed and in an ongoing fashion. Interventional radiology's major identity problem will require multiple corrective measures, including a name change. Diagnostic radiologists must fully embrace the concept of the dedicated interventionalist. Interspecialty turf battles will continue, especially with cardiologists and vascular surgeons. To advance the discipline, interventional radiologists must remain involved in cutting-edge therapies such as endograft repair of aortic aneurysms and carotid stent placement. As the population ages, interventionalists will experience a shift toward a greater emphasis on cancer treatment. Political agendas and public pressure will improve access to care and result in managed health care reforms. Academic centers will continue to witness a decline in time and resources available to pursue academic missions. The public outcry for accountability will result in systems changes aimed at reducing errors and process changes in the way physicians are trained, certified, and monitored. Evidence-based medicine will be the watchword of this century. Interventional radiology will maintain its role through development of methods for delivery of genes, gene products, and drugs to specific target sites; control of angiogenesis and other biologic processes; and noninvasive image-guided delivery of various forms of energy for ablation.

The Reintegration of Tongan Postgraduate Scholars after Study Abroad: Knowledge Utilisation and Resituation

Science.gov (United States)

Franken, Margaret; Langi, Nautalus Tuituiovai Kaho; Branson, Christopher

2016-01-01

Higher education has seen increasing educational mobility as students finance themselves or get financial support from their families to study abroad (Shields "Comp Educ Rev" 57(4):609-636, 2013; Verbik and Lazanowski in "World education news and reviews." http://www.wes.org/educators/pdf/StudentMobility.pdf, 2007). Another…

O uso de técnicas vocais como recursos retóricos na construção do discurso

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Maria Ignez de Lima PEDROSO

2008-12-01

Full Text Available As técnicas vocais são um conjunto de procedimentos facilitadores da voz que podem interferir na qualidade vocal dos sujeitos. O conhecimento atualizado, desses procedimentos, por meio de um estudo linguístico-discursivo é imprescindível para a atuação em Fonoaudiologia Estética, que pode abranger em seus trabalhos a oratória. Esses fatores motivaram-me, primeiramente, a fazer um levantamento bibliográfico sobre as técnicas vocais para os diversos profissionais da voz falada e cantada, estudo que possibilitou a organização de uma coletânea das principais técnicas pesquisadas. Tomando essa pesquisa como ponto de partida, neste trabalho, minha proposta é apresentar uma reflexão e discussão focadas no uso das técnicas relacionadas, principalmente, à ação harmônica da conduta fonatória, que estão fundamentadas nos seguintes aspectos: relaxamento, respiração, articulação, projeção, flexibilidade vocal. Nessa discussão, saliento a importância da voz e de vários componentes linguísticos da dinâmica vocal (frequência, intensidade, entonação, ritmo e velocidade de fala, entre outros elementos prosódicos que, nos processos dialógico-argumentativos da oratória, funcionam como recursos persuasivos e de veridicção na construção do discurso de diversos profissionais da voz falada, tais como advogados, professores, pastores, vendedores, locutores e repórteres, dentre outros.

O uso de técnicas vocais como recursos retóricos na construção do discurso

Directory of Open Access Journals (Sweden)

Maria Ignez de Lima PEDROSO

2013-10-01

Full Text Available As técnicas vocais são um conjunto de procedimentos facilitadores da voz que podem interferir na qualidade vocal dos sujeitos. O conhecimento atualizado, desses procedimentos, por meio de um estudo linguístico-discursivo é imprescindível para a atuação em Fonoaudiologia Estética, que pode abranger em seus trabalhos a oratória. Esses fatores motivaram-me, primeiramente, a fazer um levantamento bibliográfico sobre as técnicas vocais para os diversos profissionais da voz falada e cantada, estudo que possibilitou a organização de uma coletânea das principais técnicas pesquisadas. Tomando essa pesquisa como ponto de partida, neste trabalho, minha proposta é apresentar uma reflexão e discussão focadas no uso das técnicas relacionadas, principalmente, à ação harmônica da conduta fonatória, que estão fundamentadas nos seguintes aspectos: relaxamento, respiração, articulação, projeção, flexibilidade vocal. Nessa discussão, saliento a importância da voz e de vários componentes linguísticos da dinâmica vocal (frequência, intensidade, entonação, ritmo e velocidade de fala, entre outros elementos prosódicos que, nos processos dialógico-argumentativos da oratória, funcionam como recursos persuasivos e de veridicção na construção do discurso de diversos profissionais da voz falada, tais como advogados, professores, pastores, vendedores, locutores e repórteres, dentre outros.

Meteorología clásica en imágenes de la última época de la Antigüedad, ilustrada con ejemplos sacados de Gregorio Nacianceno

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Manfred Kertsch

1980-06-01

Full Text Available Using the imagery of Gregory of Nazianzus as starting point, the author tries to show that the doxographical example in Gregory’s Second Theological Oration (Or. XXVIII 26, PG 36, 61 C-64A, in combination with several other similar specimina, furnished by late Antiquity, may help resolve the problem raised by Quidam existimant at Seneca, Natur. quaest. III 24, 4. Who is meant here by quidam? In the author’s opinion: primarily Posidonius. In addition, this paper stresses the general significance and usefulness of late doxographical texts for reconstructing some details of the lost physical Science of the classical period.

"SOCRATICS" AS ADDRESSES OF ISOCRATES’ EPIDEICTIC SPEECHES (Against the Sophists, Encomium of Helen, Busiris

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Anna Usacheva

2012-06-01

Full Text Available This article analyses the three epideictic orations of Isocrates which are in themselves a precious testimony of the quality of intellectual life at the close of the fourth century before Christ. To this period belong also the Socratics who are generally seen as an important link between Socrates and Plato. The author of this article proposes a more productive approach to the study of Antisthenes, Euclid of Megara and other so-called Socratics, revealing them not as independent thinkers but rather as adherents of the sophistic school and also as teachers, thereby, including them among those who took part in the educative activity of their time

Entre la laudatio y la plegaria: la adlocutio sponsalis en los epitalamios neolatinos

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Antonio Serrano Cueto

2013-10-01

Full Text Available The poetic tradition has established the so-called adlocutio sponsalis at the end of the epithalamia as a common topic. Here the poet, or a divinity (frequently the goddess Venus, adresses the couple to incite them to sexual union and to wish them everlasting love, harmony, happiness, prosperity and descendants. The epideictic rhetoric for the nuptial subject already prescribed the orator to wish these desiderata, especially gathered in a prayer to the gods. In the Latin epithalamia of the 15th-16th centuries we can see some variations of the adlocutio ─sometimes shaped as a Christian prayer─ that emphasize the laudatory features inherited from Antiquity.

Tycho Brahe

Science.gov (United States)

Dreyer, John Louis Emil

2014-02-01

Preface; 1. The revival of astronomy in Europe; 2. Tycho Brahe's youth; 3. The new star of 1572; 4. Tycho's oration on astrology and his travels in 1575; 5. The island of Hveen and Tycho Brahe's observatories and other buildings; 6. Tycho's life at Hveen until the death of King Frederick II; 7. Tycho's book on the comet of 1577, and his system of the world; 8. Further work on the star of 1572; 9. The last years at Hveen, 1588-97; 10. Tycho's life from his leaving Hveen until his arrival at Prague; 11. Tycho Brahe in Bohemia - his death; 12. Tycho Brahe's scientific achievements; Appendix; Notes; Index.

Global Malmquist indices of productivity change in Egyptian wheat production

Energy Technology Data Exchange (ETDEWEB)

Elasraag, Y.H.; Alarcón, S.

2017-07-01

This study aims to measure the total factor productivity of the main govern orates of wheat production in Egypt during the time period 1990-2012 and decompose it into technical change, efficiency change and scale change. We used Global Malmquist TFP index as a non-parametric approach. The results indicated that the contribution of technical change component is more important than the efficiency change component. In fact technical change rose, 25.7%, while efficiency change presented a little decline, 3.7%. The decomposition of efficiency change indicated that the main problem of wheat production in Egypt was scale efficiency that worsened by 5.5%.

L’éloquence de la chaire à l’époque romantique : le cas de Lacordaire et de Lamennais

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Marta Sukiennicka

2015-12-01

Full Text Available This paper considers French ecclesiastical rhetoric in the Romantic era, focusing on Lacordaire’s and Lamennais’ contrasting views on the role of eloquence in religious discourse. It argues that Lacordaire, despite employing secular language in his Conférences remains a classicist religious orator, whereas Lammenais expresses his deep distrust of the spoken word and condemns eloquence, turning to letters and political discourse. The comparison of the two concepts can be seen as an exemplification of the transition from littérature-discours to littérature-texte, a general phenomenon in the French Romantic literature as described by Alain Vaillant.

De la palabra-acción a la palabra-imitación: itinerario retórico de Cicerón

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Carlos Lévy

2012-12-01

Full Text Available This paper aims to show how Cicero's consideration of eloquence as imitation was a late decision in his life caused by the circumstances. The expression "Ciceronian challenge" refers here to the conversion from a rhetoric based on the concept of force to a rhetoric where the concept of imitation has gained greater importance. Although during the early years of his career as orator, Cicero favored the representation of the spoken word as illocutionary and perlocutionary force -as in Austin's terms -, towards the end of his life he took a more abstract position in which the concept of imitation finally prevailed as a key word in his rhetoric.

Tjazhelovessõ Gollivuda v deistvii / Jevgeni Levik

Index Scriptorium Estoniae

Levik, Jevgeni

2005-01-01

Koguperefilm "Lemony Snicketi sari õnnetuid lugusid" ("Lemony Snicket's A Series of Unfortunate Events") : režissöör Brad Silberling : Ameerika Ühendriigid 2004 ja seikluslik komöödia "Steve Zissou ja veealune maailm" ("Life Aquatic with Steve Zissou") : režissöör Wes Anderson : Ameerika Ühendriigid 2004

The Danish organic movement from social movement to market mainstream and beyond …?

DEFF Research Database (Denmark)

Kjeldsen, Chris; Ingemann, Jan Holm

2010-01-01

The development of organic and with them various other forms of alternative food networks have been the subject of extensive research within the field of agro-food studies during the past 10–20 years. In that period, organic food has gained an increasing food market share and a wide number of Wes...

Two bifunctional enzymes from the marine protist Thraustochytrium roseum: biochemical characterization of wax ester synthase/acyl-CoA:diacylglycerol acyltransferase activity catalyzing wax ester and triacylglycerol synthesis.

Science.gov (United States)

Zhang, Nannan; Mao, Zejing; Luo, Ling; Wan, Xia; Huang, Fenghong; Gong, Yangmin

2017-01-01

Triacylglycerols (TAGs) and wax esters (WEs) are important neutral lipids which serve as energy reservoir in some plants and microorganisms. In recent years, these biologically produced neutral lipids have been regarded as potential alternative energy sources for biofuel production because of the increased interest on developing renewable and environmentally benign alternatives for fossil fuels. In bacteria, the final step in TAG and WE biosynthetic pathway is catalyzed by wax ester synthase/acyl coenzyme A (acyl-CoA):diacylglycerol acyltransferase (WS/DGAT). This bifunctional WS/DGAT enzyme is also a key enzyme in biotechnological production of liquid WE via engineering of plants and microorganisms. To date, knowledge about this class of biologically and biotechnologically important enzymes is mainly from biochemical characterization of WS/DGATs from Arabidopsis, jojoba and some bacteria that can synthesize both TAGs and WEs intracellularly, whereas little is known about WS/DGATs from eukaryotic microorganisms. Here, we report the identification and characterization of two bifunctional WS/DGAT enzymes (designated TrWSD4 and TrWSD5) from the marine protist Thraustochytrium roseum . Both TrWSD4 and TrWSD5 comprise a WS-like acyl-CoA acyltransferase domain and the recombinant proteins purified from Escherichia coli Rosetta (DE3) have substantial WS and lower DGAT activity. They exhibit WS activity towards various-chain-length saturated and polyunsaturated acyl-CoAs and fatty alcohols ranging from C 10 to C 18 . TrWSD4 displays WS activity with the lowest K m value of 0.14 μM and the highest k cat / K m value of 1.46 × 10 5  M -1  s -1 for lauroyl-CoA (C 12:0 ) in the presence of 100 μM hexadecanol, while TrWSD5 exhibits WS activity with the lowest K m value of 0.96 μM and the highest k cat / K m value of 9.83 × 10 4  M -1  s -1 for decanoyl-CoA (C 10:0 ) under the same reaction condition. Both WS/DGAT enzymes have the highest WS activity at 37 and 47�

Ethical issues in consumer genome sequencing: Use of consumers' samples and data.

Science.gov (United States)

Niemiec, Emilia; Howard, Heidi Carmen

2016-03-01

High throughput approaches such as whole genome sequencing (WGS) and whole exome sequencing (WES) create an unprecedented amount of data providing powerful resources for clinical care and research. Recently, WGS and WES services have been made available by commercial direct-to-consumer (DTC) companies. The DTC offer of genetic testing (GT) has already brought attention to potentially problematic issues such as the adequacy of consumers' informed consent and transparency of companies' research activities. In this study, we analysed the websites of four DTC GT companies offering WGS and/or WES with regard to their policies governing storage and future use of consumers' data and samples. The results are discussed in relation to recommendations and guiding principles such as the "Statement of the European Society of Human Genetics on DTC GT for health-related purposes" (2010) and the "Framework for responsible sharing of genomic and health-related data" (Global Alliance for Genomics and Health, 2014). The analysis reveals that some companies may store and use consumers' samples or sequencing data for unspecified research and share the data with third parties. Moreover, the companies do not provide sufficient or clear information to consumers about this, which can undermine the validity of the consent process. Furthermore, while all companies state that they provide privacy safeguards for data and mention the limitations of these, information about the possibility of re-identification is lacking. Finally, although the companies that may conduct research do include information regarding proprietary claims and commercialisation of the results, it is not clear whether consumers are aware of the consequences of these policies. These results indicate that DTC GT companies still need to improve the transparency regarding handling of consumers' samples and data, including having an explicit and clear consent process for research activities.

Somatic HLA mutations expose the role of class I–mediated autoimmunity in aplastic anemia and its clonal complications

Science.gov (United States)

Duke, Jamie L.; Xie, Hongbo M.; Stanley, Natasha; Atienza, Jamie; Perdigones, Nieves; Nicholas, Peter; Ferriola, Deborah; Li, Yimei; Huang, Hugh; Ye, Wenda; Morrissette, Jennifer J. D.; Kearns, Jane; Porter, David L.; Podsakoff, Gregory M.; Eisenlohr, Laurence C.; Biegel, Jaclyn A.; Chou, Stella T.; Monos, Dimitrios S.; Bessler, Monica; Olson, Timothy S.

2017-01-01

Acquired aplastic anemia (aAA) is an acquired deficiency of early hematopoietic cells, characterized by inadequate blood production, and a predisposition to myelodysplastic syndrome (MDS) and leukemia. Although its exact pathogenesis is unknown, aAA is thought to be driven by human leukocyte antigen (HLA)–restricted T cell immunity, with earlier studies favoring HLA class II-mediated pathways. Using whole-exome sequencing (WES), we recently identified 2 patients with aAA with somatic mutations in HLA class I genes. We hypothesized that HLA class I mutations are pathognomonic for autoimmunity in aAA, but were previously underappreciated because the major histocompatibility complex (MHC) region is notoriously difficult to analyze by WES. Using a combination of targeted deep sequencing of HLA class I genes and single nucleotide polymorphism array (SNP-A) genotyping, we screened 66 patients with aAA for somatic HLA class I loss. We found somatic HLA loss in 11 patients (17%), with 13 loss-of-function mutations in HLA-A*33:03, HLA-A*68:01, HLA-B*14:02, and HLA-B*40:02 alleles. Three patients had more than 1 mutation targeting the same HLA allele. Interestingly, HLA-B*14:02 and HLA-B*40:02 were significantly overrepresented in patients with aAA compared with ethnicity-matched controls. Patients who inherited the targeted HLA alleles, regardless of HLA mutation status, had a more severe disease course with more frequent clonal complications as assessed by WES, SNP-A, and metaphase cytogenetics, and more frequent secondary MDS. The finding of recurrent HLA class I mutations provides compelling evidence for a predominant HLA class I-driven autoimmunity in aAA and establishes a novel link between immunogenetics and clonal evolution of patients with aAA. PMID:28971166

Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene.

Science.gov (United States)

Bonnefond, Amélie; Philippe, Julien; Durand, Emmanuelle; Dechaume, Aurélie; Huyvaert, Marlène; Montagne, Louise; Marre, Michel; Balkau, Beverley; Fajardy, Isabelle; Vambergue, Anne; Vatin, Vincent; Delplanque, Jérôme; Le Guilcher, David; De Graeve, Franck; Lecoeur, Cécile; Sand, Olivier; Vaxillaire, Martine; Froguel, Philippe

2012-01-01

Maturity-onset of the young (MODY) is a clinically heterogeneous form of diabetes characterized by an autosomal-dominant mode of inheritance, an onset before the age of 25 years, and a primary defect in the pancreatic beta-cell function. Approximately 30% of MODY families remain genetically unexplained (MODY-X). Here, we aimed to use whole-exome sequencing (WES) in a four-generation MODY-X family to identify a new susceptibility gene for MODY. WES (Agilent-SureSelect capture/Illumina-GAIIx sequencing) was performed in three affected and one non-affected relatives in the MODY-X family. We then performed a high-throughput multiplex genotyping (Illumina-GoldenGate assay) of the putative causal mutations in the whole family and in 406 controls. A linkage analysis was also carried out. By focusing on variants of interest (i.e. gains of stop codon, frameshift, non-synonymous and splice-site variants not reported in dbSNP130) present in the three affected relatives and not present in the control, we found 69 mutations. However, as WES was not uniform between samples, a total of 324 mutations had to be assessed in the whole family and in controls. Only one mutation (p.Glu227Lys in KCNJ11) co-segregated with diabetes in the family (with a LOD-score of 3.68). No KCNJ11 mutation was found in 25 other MODY-X unrelated subjects. Beyond neonatal diabetes mellitus (NDM), KCNJ11 is also a MODY gene ('MODY13'), confirming the wide spectrum of diabetes related phenotypes due to mutations in NDM genes (i.e. KCNJ11, ABCC8 and INS). Therefore, the molecular diagnosis of MODY should include KCNJ11 as affected carriers can be ideally treated with oral sulfonylureas.

Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene.

Directory of Open Access Journals (Sweden)

Amélie Bonnefond

Full Text Available BACKGROUND: Maturity-onset of the young (MODY is a clinically heterogeneous form of diabetes characterized by an autosomal-dominant mode of inheritance, an onset before the age of 25 years, and a primary defect in the pancreatic beta-cell function. Approximately 30% of MODY families remain genetically unexplained (MODY-X. Here, we aimed to use whole-exome sequencing (WES in a four-generation MODY-X family to identify a new susceptibility gene for MODY. METHODOLOGY: WES (Agilent-SureSelect capture/Illumina-GAIIx sequencing was performed in three affected and one non-affected relatives in the MODY-X family. We then performed a high-throughput multiplex genotyping (Illumina-GoldenGate assay of the putative causal mutations in the whole family and in 406 controls. A linkage analysis was also carried out. PRINCIPAL FINDINGS: By focusing on variants of interest (i.e. gains of stop codon, frameshift, non-synonymous and splice-site variants not reported in dbSNP130 present in the three affected relatives and not present in the control, we found 69 mutations. However, as WES was not uniform between samples, a total of 324 mutations had to be assessed in the whole family and in controls. Only one mutation (p.Glu227Lys in KCNJ11 co-segregated with diabetes in the family (with a LOD-score of 3.68. No KCNJ11 mutation was found in 25 other MODY-X unrelated subjects. CONCLUSIONS/SIGNIFICANCE: Beyond neonatal diabetes mellitus (NDM, KCNJ11 is also a MODY gene ('MODY13', confirming the wide spectrum of diabetes related phenotypes due to mutations in NDM genes (i.e. KCNJ11, ABCC8 and INS. Therefore, the molecular diagnosis of MODY should include KCNJ11 as affected carriers can be ideally treated with oral sulfonylureas.

A pilot study on the effects of a team building process on the perception of work environment in an integrative hospital for neurological rehabilitation

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Büssing Arndt

2010-03-01

Full Text Available Abstract Background Neurological rehabilitation is one of the most care-intensive challenges in the health care system requiring specialist therapeutic and nursing knowledge. In this descriptive pilot study, we investigated the effects of a team building process on perceived work environment, self-ascribed professional competence, life satisfaction, and client satisfaction in an anthroposophic specialized hospital for neurological rehabilitation. The team-building process consisted of didactic instruction and training in problem-solving, teambuilding and constructive conflict resolution. Methods Seventy seven staff members and 44 patients' relatives were asked to complete a survey that included the Work Environment Scale (WES-10, a Life Satisfaction Scale (BMLSS, the Conviction of Therapeutic Competency (CTC scale and the Client Satisfaction Questionnaire (CSQ-8. To evaluate the outcome of the team building process, we analyzed changes over time in the WES-10 subscales. Additionally the interrelationship between the WES-10 subscales with other subscales and with sociodemographic parameters like age, gender was calculated by means of a bivariate correlation analysis. Results The team building process had a significant positive effect on perceived work environment in only one area. There was a significant improvement in the ward staffs' perception of their ability to constructively resolve conflicts 3 years after inception of the team building process than there was before inception. However, even in a unit that utilized holistic treatment and nursing in the care of severely disable patients, such care necessitating a very heavy workload, the measurements on the Self Realization, Life Satisfaction and Conviction of Therapeutic Competency scales remained high and unchanged over the three year time period of the study. Conclusions Strategic interventions might be an option to improve interpersonal relationships and finally quality of patient care.

Application of Whole Exome Sequencing in Six Families with an Initial Diagnosis of Autosomal Dominant Retinitis Pigmentosa: Lessons Learned

Science.gov (United States)

Fernandez-San Jose, Patricia; Liu, Yichuan; March, Michael; Pellegrino, Renata; Golhar, Ryan; Corton, Marta; Blanco-Kelly, Fiona; López-Molina, Maria Isabel; García-Sandoval, Blanca; Guo, Yiran; Tian, Lifeng; Liu, Xuanzhu; Guan, Liping; Zhang, Jianguo; Keating, Brendan; Xu, Xun

2015-01-01

This study aimed to identify the genetics underlying dominant forms of inherited retinal dystrophies using whole exome sequencing (WES) in six families extensively screened for known mutations or genes. Thirty-eight individuals were subjected to WES. Causative variants were searched among single nucleotide variants (SNVs) and insertion/deletion variants (indels) and whenever no potential candidate emerged, copy number variant (CNV) analysis was performed. Variants or regions harboring a candidate variant were prioritized and segregation of the variant with the disease was further assessed using Sanger sequencing in case of SNVs and indels, and quantitative PCR (qPCR) for CNVs. SNV and indel analysis led to the identification of a previously reported mutation in PRPH2. Two additional mutations linked to different forms of retinal dystrophies were identified in two families: a known frameshift deletion in RPGR, a gene responsible for X-linked retinitis pigmentosa and p.Ser163Arg in C1QTNF5 associated with Late-Onset Retinal Degeneration. A novel heterozygous deletion spanning the entire region of PRPF31 was also identified in the affected members of a fourth family, which was confirmed with qPCR. This study allowed the identification of the genetic cause of the retinal dystrophy and the establishment of a correct diagnosis in four families, including a large heterozygous deletion in PRPF31, typically considered one of the pitfalls of this method. Since all findings in this study are restricted to known genes, we propose that targeted sequencing using gene-panel is an optimal first approach for the genetic screening and that once known genetic causes are ruled out, WES might be used to uncover new genes involved in inherited retinal dystrophies. PMID:26197217

Ethical issues in consumer genome sequencing: Use of consumers' samples and data

Directory of Open Access Journals (Sweden)

Emilia Niemiec

2016-03-01

Full Text Available High throughput approaches such as whole genome sequencing (WGS and whole exome sequencing (WES create an unprecedented amount of data providing powerful resources for clinical care and research. Recently, WGS and WES services have been made available by commercial direct-to-consumer (DTC companies. The DTC offer of genetic testing (GT has already brought attention to potentially problematic issues such as the adequacy of consumers' informed consent and transparency of companies' research activities. In this study, we analysed the websites of four DTC GT companies offering WGS and/or WES with regard to their policies governing storage and future use of consumers' data and samples. The results are discussed in relation to recommendations and guiding principles such as the “Statement of the European Society of Human Genetics on DTC GT for health-related purposes” (2010 and the “Framework for responsible sharing of genomic and health-related data” (Global Alliance for Genomics and Health, 2014. The analysis reveals that some companies may store and use consumers' samples or sequencing data for unspecified research and share the data with third parties. Moreover, the companies do not provide sufficient or clear information to consumers about this, which can undermine the validity of the consent process. Furthermore, while all companies state that they provide privacy safeguards for data and mention the limitations of these, information about the possibility of re-identification is lacking. Finally, although the companies that may conduct research do include information regarding proprietary claims and commercialisation of the results, it is not clear whether consumers are aware of the consequences of these policies. These results indicate that DTC GT companies still need to improve the transparency regarding handling of consumers' samples and data, including having an explicit and clear consent process for research activities.

Somatic HLA Mutations Expose the Role of Class I-Mediated Autoimmunity in Aplastic Anemia and its Clonal Complications.

Science.gov (United States)

Babushok, Daria V; Duke, Jamie L; Xie, Hongbo M; Stanley, Natasha; Atienza, Jamie; Perdigones, Nieves; Nicholas, Peter; Ferriola, Deborah; Li, Yimei; Huang, Hugh; Ye, Wenda; Morrissette, Jennifer J D; Kearns, Jane; Porter, David L; Podsakoff, Gregory M; Eisenlohr, Laurence C; Biegel, Jaclyn A; Chou, Stella T; Monos, Dimitrios S; Bessler, Monica; Olson, Timothy S

2017-10-10

Acquired aplastic anemia (aAA) is an acquired deficiency of early hematopoietic cells, characterized by inadequate blood production, and a predisposition to myelodysplastic syndrome (MDS) and leukemia. Although its exact pathogenesis is unknown, aAA is thought to be driven by Human Leukocyte Antigen (HLA)-restricted T cell immunity, with earlier studies favoring HLA class II-mediated pathways. Using whole exome sequencing (WES), we recently identified two aAA patients with somatic mutations in HLA class I genes. We hypothesized that HLA class I mutations are pathognomonic for autoimmunity in aAA, but were previously underappreciated because the Major Histocompatibility Complex (MHC) region is notoriously difficult to analyze by WES. Using a combination of targeted deep sequencing of HLA class I genes and single nucleotide polymorphism array (SNP-A) genotyping we screened 66 aAA patients for somatic HLA class I loss. We found somatic HLA loss in eleven patients (17%), with thirteen loss-of-function mutations in HLA-A *33:03, HLA-A *68:01, HLA-B *14:02 and HLA-B *40:02 alleles. Three patients had more than one mutation targeting the same HLA allele. Interestingly, HLA-B *14:02 and HLA-B *40:02 were significantly overrepresented in aAA patients, compared to ethnicity-matched controls. Patients who inherited the targeted HLA alleles, regardless of HLA mutation status, had a more severe disease course with more frequent clonal complications as assessed by WES, SNP-A, and metaphase cytogenetics, and more frequent secondary MDS. The finding of recurrent HLA class I mutations provides compelling evidence for a predominant HLA class I-driven autoimmunity in aAA, and establishes a novel link between aAA patients' immunogenetics and clonal evolution.

Rhabdosargus holubi Rhabdosargus globiceps

African Journals Online (AJOL)

Bioi. 17: 143-162. CARR, W.E.S. & ADAMS, C.A. 1973. Food habits of juvenile marine fishes occupying seagrass beds in the estuarine zone near. Crystal River, Florida. Trans. A mer. Fish. Soc. 3: 511- 540. CHARLES, R. 1975. Aspects of the biology of the mojarra. Eucinostomus gula (Quoy & Gaimard), in the Biscayne Bay,.

Recycling Waste Electrical Socket as a Carbon Resource in ...

African Journals Online (AJOL)

Composite pellets of medium grade Agbaja iron ore (assaying ~74 % Fe2O3) with WES were irradiated in a domestic microwave oven (Pioneer, Model PM-25 L, 2450 MHz and 1000 W). The reduced mass was characterised by XRD and SEM/EDS analyses and the extent of reduction after 40 min was determined.

Whole-exome sequencing for diagnosis of hereditary ichthyosis.

Science.gov (United States)

Sitek, J C; Kulseth, M A; Rypdal, K B; Skodje, T; Sheng, Y; Retterstøl, L

2018-02-14

Hereditary ichthyosis constitutes a diverse group of cornification disorders. Identification of the molecular cause facilitates optimal patient care. We wanted to estimate the diagnostic yield of applying whole-exome sequencing (WES) in the routine genetic workup of inherited ichthyosis. During a 3-year-period, all ichthyosis patients, except X-linked and mild vulgar ichthyosis, consecutively admitted to a university hospital clinic were offered WES with subsequent analysis of ichthyosis-related genes as a first-line genetic investigation. Clinical and molecular data have been collected retrospectively. Genetic variants causative for the ichthyosis were identified in 27 of 34 investigated patients (79.4%). In all, 31 causative mutations across 13 genes were disclosed, including 12 novel variants. TGM1 was the most frequently mutated gene, accounting for 43.7% of patients suffering from autosomal recessive congenital ichthyosis (ARCI). Whole-exome sequencing appears an effective tool in disclosing the molecular cause of patients with hereditary ichthyosis seen in clinical practice and should be considered a first-tier genetic test in these patients. © 2018 European Academy of Dermatology and Venereology.

Clinical pharmacogenomics testing in the era of next generation sequencing: challenges and opportunities for precision medicine.

Science.gov (United States)

Ji, Yuan; Si, Yue; McMillin, Gwendolyn A; Lyon, Elaine

2018-04-23

The rapid development and dramatic decrease in cost of sequencing techniques have ushered the implementation of genomic testing in patient care. Next generation DNA sequencing (NGS) techniques have been used increasingly in clinical laboratories to scan the whole or part of the human genome in order to facilitate diagnosis and/or prognostics of genetic disease. Despite many hurdles and debates, pharmacogenomics (PGx) is believed to be an area of genomic medicine where precision medicine could have immediate impact in the near future. Areas covered: This review focuses on lessons learned through early attempts of clinically implementing PGx testing; the challenges and opportunities that PGx testing brings to precision medicine in the era of NGS. Expert commentary: Replacing targeted analysis approach with NGS for PGx testing is neither technically feasible nor necessary currently due to several technical limitations and uncertainty involved in interpreting variants of uncertain significance for PGx variants. However, reporting PGx variants out of clinical whole exome or whole genome sequencing (WES/WGS) might represent additional benefits for patients who are tested by WES/WGS.

De Novo Truncating Mutations in AHDC1 in Individuals with Syndromic Expressive Language Delay, Hypotonia, and Sleep Apnea

Science.gov (United States)

Xia, Fan; Bainbridge, Matthew N.; Tan, Tiong Yang; Wangler, Michael F.; Scheuerle, Angela E.; Zackai, Elaine H.; Harr, Margaret H.; Sutton, V. Reid; Nalam, Roopa L.; Zhu, Wenmiao; Nash, Margot; Ryan, Monique M.; Yaplito-Lee, Joy; Hunter, Jill V.; Deardorff, Matthew A.; Penney, Samantha J.; Beaudet, Arthur L.; Plon, Sharon E.; Boerwinkle, Eric A.; Lupski, James R.; Eng, Christine M.; Muzny, Donna M.; Yang, Yaping; Gibbs, Richard A.

2014-01-01

Clinical whole-exome sequencing (WES) for identification of mutations leading to Mendelian disease has been offered to the medical community since 2011. Clinically undiagnosed neurological disorders are the most frequent basis for test referral, and currently, approximately 25% of such cases are diagnosed at the molecular level. To date, there are approximately 4,000 “known” disease-associated loci, and many are associated with striking dysmorphic features, making genotype-phenotype correlations relatively straightforward. A significant fraction of cases, however, lack characteristic dysmorphism or clinical pathognomonic traits and are dependent upon molecular tests for definitive diagnoses. Further, many molecular diagnoses are guided by recent gene-disease association discoveries. Hence, there is a critical interplay between clinical testing and research leading to gene-disease association discovery. Here, we describe four probands, all of whom presented with hypotonia, intellectual disability, global developmental delay, and mildly dysmorphic facial features. Three of the four also had sleep apnea. Each was a simplex case without a remarkable family history. Using WES, we identified AHDC1 de novo truncating mutations that most likely cause this genetic syndrome. PMID:24791903

De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder

Science.gov (United States)

Dong, Shan; Walker, Michael F.; Carriero, Nicholas J.; DiCola, Michael; Willsey, A. Jeremy; Ye, Adam Y.; Waqar, Zainulabedin; Gonzalez, Luis E.; Overton, John D.; Frahm, Stephanie; Keaney, John F.; Teran, Nicole A.; Dea, Jeanselle; Mandell, Jeffrey D.; Bal, Vanessa Hus; Sullivan, Catherine A.; DiLullo, Nicholas M.; Khalil, Rehab O.; Gockley, Jake; Yuksel, Zafer; Sertel, Sinem M.; Ercan-Sencicek, A. Gulhan; Gupta, Abha R.; Mane, Shrikant M.; Sheldon, Michael; Brooks, Andrew I.; Roeder, Kathryn; Devlin, Bernie; State, Matthew W.; Wei, Liping; Sanders, Stephan J.

2014-01-01

SUMMARY Whole-exome sequencing (WES) studies have demonstrated the contribution of de novo loss-of-function single nucleotide variants to autism spectrum disorders (ASD). However, challenges in the reliable detection of de novo insertions and deletions (indels) have limited inclusion of these variants in prior analyses. Through the application of a robust indel detection method to WES data from 787 ASD families (2,963 individuals), we demonstrate that de novo frameshift indels contribute to ASD risk (OR=1.6; 95%CI=1.0-2.7; p=0.03), are more common in female probands (p=0.02), are enriched among genes encoding FMRP targets (p=6×10−9), and arise predominantly on the paternal chromosome (p<0.001). Based on mutation rates in probands versus unaffected siblings, de novo frameshift indels contribute to risk in approximately 3.0% of individuals with ASD. Finally, through observing clustering of mutations in unrelated probands, we report two novel ASD-associated genes: KMT2E (MLL5), a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release. PMID:25284784

KIF16B is a candidate gene for a novel autosomal-recessive intellectual disability syndrome.

Science.gov (United States)

Alsahli, Saud; Arold, Stefan T; Alfares, Ahmed; Alhaddad, Bader; Al Balwi, Mohammed; Kamsteeg, Erik-Jan; Al-Twaijri, Waleed; Alfadhel, Majid

2018-05-07

Intellectual disability (ID) and global developmental delay are closely related; the latter is reserved for children under the age of 5 years as it is challenging to reliably assess clinical severity in this population. ID is a common condition, with up to 1%-3% of the population being affected and leading to a huge social and economic impact. ID is attributed to genetic abnormalities most of the time; however, the exact role of genetic involvement in ID is yet to be determined. Whole exome sequencing (WES) has gained popularity in the workup for ID, and multiple studies have been published examining the diagnostic yield in identification of the disease-causing variant (16%-55%), with the genetic involvement increasing as intelligence quotient decreases. WES has also accelerated novel disease gene discovery in this field. We identified a novel biallelic variant in the KIF16B gene (NM_024704.4:c.3611T > G) in two brothers that may be the cause of their phenotype. © 2018 Wiley Periodicals, Inc.

On the method for fracture strength assessment. Part 2; Kozobutsu no hakai kyodo hyoka no jissai. 2

Energy Technology Data Exchange (ETDEWEB)

Onozuka, M. [Ishikawajima-Harima Heavy Industries Co. Ltd., Tokyo (Japan)

1995-09-05

In order to reduce the economic cost of the generating set etc. the damages to the materials and structures of the structure to last the original design life were observed and it was considered that if damages were fewer the life would be longer. One of the important items in assessing, amending and renewing the rationality of the established structure is the assessment of the defects and flaws existing in the welded joints. In Japan, WES 2805 which is named as the Method for Assessing the Defects for the Brittle Fracture Occurring Properties of Welded Joint was formulated in 1980 as the standard of the Japan Welding Society. Although it has been applied as the criterion in wide range, the part on brittle fracture is now under revision to reflect the research results on fracture mechanics thereafter and to perfect the fracture relationship because many years have passed since its first formulation. In this paper, the contents in the final stage of the revision of WES 2805 standard, including concrete examples, were introduced. 2 refs., 6 figs., 2 tabs.

Characterizing the Performance of the Wheel Electrostatic Spectrometer

Science.gov (United States)

Johansen, Michael R.; Mackey, P. J.; Holbert, E.; Calle, C. I.; Clements, J. S.

2013-01-01

Insulators need to be discharged after each wheel revolution. Sensor responses repeatable within one standard deviation in the noise of the signal. Insulators may not need to be cleaned after each revolution. Parent Technology- Mars Environmental Compatibility Assessment/Electrometer Electrostatic sensors with dissimilar cover insulators Protruding insulators tribocharge against regolith simulant Developed for use on the scoop for the 2001 Mars Odyssey lander Wheel Electrostatic Spectrometer Embedded electrostatic sensors in prototype Martian rover wheel If successful, this technology will enable constant electrostatic testing on Mars Air ionizing fan used to neutralize the surface charge on cover insulators . WES rolled on JSClA lunar simulant Control experiment -Static elimination not conducted between trials -Capacitor discharged after each experiment Charge neutralization experiment -Static elimination conducted between trials -Capacitor discharged after each experiment. Air ionizing fan used on insulators after each wheel revolution Capacitor discharged after each trial Care was taken to roll WES with same speed/pressure Error bars represent one standard deviation in the noise of e ach sensor

Designing Efficient Self-Diagnosis Activities in the Physics Classroom

Science.gov (United States)

Safadi, Rafi'

2017-01-01

Self-diagnosis (SD) activities require students to self-diagnose their solutions to problems that they solved on their own. This involves identifying where they went wrong and then explaining the nature of their errors--why they went wrong--aided by some form of support. Worked examples (WEs) are often used to support students in SD activities. A…

Management Plan for the Disposal of Contaminated Material in the Craney Island Dredged Material Management Area

Science.gov (United States)

1993-09-01

1987; Westerdahl and Skogerboe 1982). ri. II L I-AINFALL ~ - n A0 J `-LOW CONTROLLERSfL I ý’-DRAIN OUTL-ET SCALE 10 2m Figure 3-8. Schematic of WES...Agency. (1986). "Quality criteria for water 1986," EPA 440/5-86-001, Washington, DC. Westerdahl , H. E., and Skogerboe, J. G. (1982). "Realistic

Teaching English or Producing Docility? Foucauldian Analysis of Pakistani State-Mandated English Textbooks

Science.gov (United States)

Channa, Liaquat Ali; Gilhooly, Daniel; Channa, Abdul Razaque; Manan, Syed Abdul

2017-01-01

The scholarship of language education, particularly with reference to learning and use of English, is marked by varieties of English. One may note two broad models: (1) ENL, ESL, and EFL; (2) EIL, ELF, and WEs. Although the scholarship is replete with debates, the debates seem to only construct and maintain that learning English and its use are…

Regional Planning, Local Visions : Participatory Futuring in West Africa

OpenAIRE

Peter Easton

2000-01-01

The note examines regional planning, and future participatory methods for economic development in West Africa, based on the work carried out by the Club du Sahel - a branch of the Organization for Economic Cooperation and Development (OECD) - responsible for coordinating northern donor agencies, in support of food security, and natural resource management in the desert-edge portions of Wes...

Performance Characteristics of Plane Wall Two Dimensional Diffusers

Science.gov (United States)

1953-02-01

die Umsetzung von Wässergeschwindigkeit in Druck . Mitt. Forsch.-Arb. Geb. Ing.-Wes., Heft 76, 1909. k6 NACA TN 2888 12. Hochschild, Heinrich...Wi 0 2/ .75 ■ /5.2s A //.00 D 7.75 • 5. 3D & \\\\ /2 /e Z d, &&3 20 24 Figure 15.- Variation of pressure efficiency with divergence angle

The Top Three Valor Awards and the United States Marine Corps: A Study from World War I to Present Day Iraq and Afghanistan

Science.gov (United States)

2014-06-13

the Medal of Honor.85 “The process by which the MOH is awarded has become flawed, and the DOD must strive to bring an end to an era of overprotection ...later in the literature review. 84Ibid., 37. 85Wes J. Deaver, “The Medal of Honor, An Era of Overprotection ,” Marine Corps Gazette 94, no. 9

PER 2009(4)

African Journals Online (AJOL)

PER Electronic Law Review - Potchefstoomse Elektroniese Regsblad

38 In Wes-Australië is die gekodifiseerde verweer van noodweer, soos vervat in die Criminal. Code, in 2008 op grond van ... 39 In Victoria word noodweer in die algemeen deur a 9AC en 9AE Crimes Act 1958 gereël, terwyl a 9AH spesifieke ...... uitg (Printing Things Potchefstroom 2005). Roth Briefing Paper No 3/07.

New players on the Dutch market for wind energy. Part 2

International Nuclear Information System (INIS)

Salverda, I.

2007-01-01

A brief overview is given of new developments in the Netherlands with respect to the wind turbine industry. In the first article on the subject attention is paid to DarwinD and Harakosan Europe. In this article a brief overview is given of two Dutch wind turbine manufacturers: Wind Energy Solutions (WES) and Emergya Wind Technology (EWT) [nl

78 FR 5837 - Notice of Lodging Proposed Consent Decree

Science.gov (United States)

2013-01-28

... Policy, 28 CFR 50.7, notice is hereby given that a proposed Consent Decree in United States v. Porter... complaint filed by the United States against Wesley Porter, Wes Porter Development Company, LLC, Temple and... Division, P.O. Box 7611, Washington, DC 20044, and refer to United States v. Porter, DJ 90-5-1-1-18341. The...

Alfabetizare politică prin lexic, instituții și modele teoretice englezești: România în a doua jumătate a secolului al XIX-lea (Political Literacy through English Lexic, Institutions and Models. Romania in the Second Hald of the 19th Century

Directory of Open Access Journals (Sweden)

Roxana PATRAȘ

2015-12-01

Full Text Available The present article endeavours to explore the political terminology of Anglo-Saxon origin, as well as to emphasize the influence of the Anglo-American political model through the analysis of some speeches delivered in various political contexts by the most appreciated Romanian orators of the 19th century. The assumption that, besides the interactions with French and German models, a third influence (the English, the British or the American may be taken into consideration has been already suggested by several historians’ research. However, our hypothesis is that the Anglo-Saxon model can be emphasized not only in the “archives” of immediate economic or diplomatic interests, but as a cultural „mediator” between the French culture’s “modelling influence” and the German culture’s “catalytic influence” (according to Lucian Blaga’s theories. The relationship between the beginning of the Romanian political civilization (the stage of political literacy and the Anglo-Saxon tradition shall be inquired from three perspectives: 1. As a step-by-step evolution; 2. As an ideal standard of political civilization; 3. As a mediation formula between opposite realities and principles (absolutism – democracy/ constitutional monarchy; centralisation – local autonomy/ federalism etc.. In the first part of the article, I propose a list of English words that are imported in the Romanian language of the 19th century and are put into circulation by the speeches delivered in the Romanian Parliament. In complementarity with the lexicographic analysis, I will emphasize the fragments where works by Edmund Burke, Benjamin Disraeli, William Ewart Gladstone, Thomas Babington Macauley, Thomas Hare, James Stuart Mill, Henry Wheaton and others are mentioned by the Romanian orators, and follow the track of their dissemination through either English originals or Romanian/ French translations.

Factores asociados a la satisfacción laboral en empleados de un hospital psiquiátrico de Bucaramanga, Colombia

Directory of Open Access Journals (Sweden)

Lucía Quintero-Isaza

2014-06-01

Full Text Available ResumenAntecedentes: Existen pocos informes sobre los factores que influyen en la satisfacción laboral de los trabajadores de la salud mental en un hospital público. Objetivo: Determinar los factores relacionados con satisfacción laboral en empleados del Hospital Psiquiátrico San Camilo de Bucaramanga, Colombia. Método: Se diseñó un estudio analítico transversal. Se solicitó la participación voluntaria de todos los trabajadores de la institución quienes diligenciaron en forma anónima un cuestionario que indagaba las características sociodemográficas, trastornos mentales comunes, trastornos de ansiedad y depresivos (Cuestionario General de Salud, GHQ-12 y satisfacción laboral (Cuestionario de Ambiente Laboral, WES-10. Un modelo de regresión lineal se calculó para controlar las correlaciones con los puntajes en el WES-10. Resultados: Un total de 217 empleados completaron en forma satisfactoria la totalidad del cuestionario. Las puntaciones para trastornos mentales comunes (β estandarizado=-0,583; t=-7,5; p<0,001 y el número de años trabajados en el hospital (β estandarizado -0,186; t=-2,6; p=0,010 mostraron una correlación significativa con el grado de satisfacción laboral. Conclusiones: Los puntajes para trastornos mentales comunes y los años laborados en la institución están significativamente correlacionados con el nivel de satisfacción laboral. (Duazary 2008; 76-81AbstractBackground: There are few reports about factors influencing the job satisfaction among healthcare employees in public hospitals. Objective: To determine the associated factors with the job satisfaction among employees of the Psychiatric Hospital San Camilo in Bucaramanga, Colombia. Method: We designed a transversal analytical study. All the employees of the institution were asked for voluntary participation. They answered anonymously a questionnaire that inquired their social-demographic characteristics, common mental illnesses, depression and

Co-"Lab"oration: A New Paradigm for Building a Management Information Systems Course

Science.gov (United States)

Breimer, Eric; Cotler, Jami; Yoder, Robert

2010-01-01

We propose a new paradigm for building a Management Information Systems course that focuses on laboratory activities developed collaboratively using Computer-Mediated Communication and Collaboration tools. A highlight of our paradigm is the "practice what you preach" concept where the computer communication tools and collaboration…

Subjective nutritional val oration generated by the patient in the hematology oncology users

International Nuclear Information System (INIS)

Andrada, D.

2004-01-01

Everybody knows that all protein calorie malnutrition is not only the cause of death in cancer patients but also affects the good performance treatment as well as their quality of life. Because of that common complication, it is necessary the use of simple tools to detect its occurrence. A recent study called NUPAC perceive that 52% of patients in advanced stages presents protein calorie malnutrition. The tool used was the subjective global valuation which is generated by the patient and is based on clinical parameters. The Eastern Cooperative Oncology Group showed that a weight loss predicts the treatment response reducing the survival and quality of life. In 2002 a study carried out in the Nutritional Support Unit, University Hospital Vall d'Hebron in Barcelona recorded that at admission only 16,7% of patients were within normal nutritional values, 38.9% were undernourished moderate and 44.4% severe malnutrition, nutritional assessment at discharge showed no significant changes in relation to income hospital. 81.2% of these patient had a prescribed diet v / o of which 43.1% needed some supplements type and only 23% an artificial diet. The valuation method used was also generated by the subjective global valuation patient. Considering the impact that the nutritional status has in the evolution of neoplastic disease we saw the need to make a job using the above tool applied by personnel out of the nutrition in order to evaluate and identify patients who need or no simple nutritional intervention. Our study was conducted in the period of August-October in 2004 and included 50 users, of both sexes (26 males and 24 females) treated with polychemotherapy (which were excluded in the first series of MDT) and either ambulatory or hospitalized at transplant unit or conventional sector in Hematology-Oncology Service at the Asociacion Espanola Primera de Socorros Mutuos. Part of the questionnaire was completed by the own user and It also were performed by anthropometric and biochemical determinations.This study allowed us to evaluate the incidence of side effects of the chemotherapy in these users

A multiproxy approach to evaluate biocidal treatm entson biodeteri orated majolica glazed tiles

OpenAIRE

Coutinho, M. L.; Miller, A. Z.; Jurado, Valme; Sáiz-Jiménez, Cesáreo; Macedo, M. F.

2016-01-01

23 páginas.-- 10 figuras.-- 6 tablas.-- 88 referencias.-- Supporting information Additional Supporting Information may be found in the online version of this article at the publisher’s web-site: http://dx.doi.org/10.1111/1462-2920.13380

Role of imaging in female infertility [Dr. K.M. Rai Memorial Oration Award

International Nuclear Information System (INIS)

Rastogi, Rajul

2010-01-01

Infertility in females is multifactorial in origin. Though hysterolaparoscopy is the gold-standard investigation, USG is usually the first-line investigation. MRI has expanded the usefulness of imaging in female infertility. This pictorial essay reviews the role of imaging in the evaluation of female infertility

The Effect of Gibberellin on Plant Growth and Development

Science.gov (United States)

1960-11-04

8217P? 1O cerh bi; ncv tnd the ntanber of berries In e-.c ch bunch. The &ver-r.j? c -vjeirht of-’a berry ::wes then derived for each bt/mchyaoD...gibberellin web strongly in evidence. In the " :* : control bunches/of the Mrran|P’variety the^er/age/weight : ,of .8. berry was 1.08 g,: fend

Incorporating big data into treatment plan evaluation: Development of statistical DVH metrics and visualization dashboards

Directory of Open Access Journals (Sweden)

Charles S. Mayo, PhD

2017-07-01

Conclusions: Statistical DVH offers an easy-to-read, detailed, and comprehensive way to visualize the quantitative comparison with historical experiences and among institutions. WES and GEM metrics offer a flexible means of incorporating discrete threshold-prioritizations and historic context into a set of standardized scoring metrics. Together, they provide a practical approach for incorporating big data into clinical practice for treatment plan evaluations.

PSU/WES interlaboratory comparative methodology study of an experimental cementitious repository seal material

International Nuclear Information System (INIS)

Roy, D.M.; Grutzeck, M.W.; Mather, K.

1980-09-01

A study is underway in two separate laboratories to investigate possible use of portland cement grout as repository sealing material for underground isolation of nuclear waste. The labs involved are the Materials Research Laboratory of the Pennsylvania State University (PSU) and the Structures Laboratory (SL) of the US Army Engineer Waterways Experiment Station. The same cementitious (grout) mixture was prepared in each laboratory in September 1980, and tests were started. Testing included characterization of cement and fly ash by chemical, physical, and petrographic procedures. Tests of hardened specimens included restrained expansion, compressive strength, modulus of elasticity, density, permeability, x-ray diffraction, and scanning electron microscopy. Each laboratory made many of the same tests and some that were not directly comparable. This document (Report 1) contains largely 3- and 7-day results and none beyond 28-day ages

oordrag van eiendomsreg in die vulgêre reg in die wes-romeinse ryk

African Journals Online (AJOL)

Mnr F Schutte

klassieke. Romeinse reg (250vC-27vC), klassieke Romeins reg (27vC-250nC), na-klassieke Romeinse reg. (250nC-1100nC). Sien verder ook Van Zyl Romeinse Privaatreg. 3 Die vulgêre reg het die klassieke reg in die tydperk tussen 350 en ...

Renal oncocytoma characterized by the defective complex I of the respiratory chain boosts the synthesis of the ROS scavenger glutathione.

Science.gov (United States)

Kürschner, Gerrit; Zhang, Qingzhou; Clima, Rosanna; Xiao, Yi; Busch, Jonas Felix; Kilic, Ergin; Jung, Klaus; Berndt, Nikolaus; Bulik, Sascha; Holzhütter, Hermann-Georg; Gasparre, Giuseppe; Attimonelli, Marcella; Babu, Mohan; Meierhofer, David

2017-12-01

Renal oncocytomas are rare benign tumors of the kidney and characterized by a deficient complex I (CI) enzyme activity of the oxidative phosphorylation (OXPHOS) system caused by mitochondrial DNA (mtDNA) mutations. Yet, little is known about the underlying molecular mechanisms and alterations of metabolic pathways in this tumor. We compared renal oncocytomas with adjacent matched normal kidney tissues on a global scale by multi-omics approaches, including whole exome sequencing (WES), proteomics, metabolomics, and metabolic pathway simulation. The abundance of proteins localized to mitochondria increased more than 2-fold, the only exception was a strong decrease in the abundance for CI subunits that revealed several pathogenic heteroplasmic mtDNA mutations by WES. We also observed renal oncocytomas to dysregulate main metabolic pathways, shunting away from gluconeogenesis and lipid metabolism. Nevertheless, the abundance of energy carrier molecules such as NAD + , NADH, NADP, ATP, and ADP were significantly higher in renal oncocytomas. Finally, a substantial 5000-fold increase of the reactive oxygen species scavenger glutathione can be regarded as a new hallmark of renal oncocytoma. Our findings demonstrate that renal oncocytomas undergo a metabolic switch to eliminate ATP consuming processes to ensure a sufficient energy supply for the tumor.

DEVELOPMENT OF WEB-BASED EXAMINATION SYSTEM USING OPEN SOURCE PROGRAMMING MODEL

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Olalere A. ABASS

2017-04-01

Full Text Available The traditional method of assessment (examination is often characterized by examination questions leakages, human errors during marking of scripts and recording of scores. The technological advancement in the field of computer science has necessitated the need for computer usage in majorly all areas of human life and endeavors, education sector not excluded. This work, Web-based Examination System (WES was, therefore, born out of the will to stymie the problems plaguing the conventional (paper-based examination system by providing a campus-wide service for e-assessment devoid of irregularities and generally fair to examinees and equally enhances instant feedback. This system developed using combination of CSS, HTML, PHP SQL MySQL and Dreamweaver is capable of reducing proportion of workload on examination, grading and reviewing on the part of examiners. Thus, the system enables the release of examination results in record time and without error. WES can serve as an effective solution for mass education evaluation and offers many novel features that cannot be implemented in paper-based systems, such as real time data collection, management and analysis, distributed and interactive assessment towards promoting distance education.

[Individualized restorative designs and clinical evaluation for dental implants in the anterior esthetic zone with inappropriate conditions].

Science.gov (United States)

Dai, Wen-yong; Zhou, Guo-xing; Zhang, Xiao-zhen; Zhao, Yi; Wang, Jie; Yang, Yi; Zhu, Zhi-jun; Tang, Chun-bo

2014-08-01

To offer individualized restorative strategies for patients receiving dental implants in the anterior esthetic zone but with inappropriate available conditions and evaluate the clinical outcomes. Forty-six patients with 58 implants were recruited for the study in accordance with the criteria and received individualized implant prostheses in the anterior esthetic zone. The patients were followed up for 3-24 months, and the clinical outcomes were evaluated by pink and white esthetic scores (PES/WES). The patients were from 18 to 69 years old, and followed up for 12.6 months in average. According to the third month follow-up esthetic scores, for PES, 1.72% of the patients got low scores, 44.83% got medium scores and 53.45% got high scores; For WES, 0% got low scores, 20.69% got medium scores and 79.31% got high scores. No implant failure or peri-implantitis occurred. Individualized restorative designs for implants in the esthetic zone can effectively improve the appearance of the prostheses which originally have no appropriate available space. Close follow-up and monitoring of the peri-implant soft tissue and proper oral hygiene instructions are important to ensure the conditions of the prostheses.

Incidentalome in Neurogenetics: Pathogenic Variant of NSD1 in a Patient With Spinocerebellar Ataxia (SCA).

Science.gov (United States)

Velasco, Harvy; Ramírez-Montaño, Diana

2018-01-01

Background: Genetic studies of late-onset sporadic ataxias (>40 years of age) are not routinely indicated. For unresolved cases, next-generation sequencing (NGS) tools, such as whole-exome sequencing (WES), are available for a definitive diagnosis. Case presentation: Our patient is a woman with a usual facial phenotype and anthropometry, who developed ataxia at 45 years of age, with no relevant family history and an initial clinical approach that ruled out common aetiologies. WES was performed when the patient was 54 years old. The results identified the heterozygous pathogenic variant c.248delA (p.N83MfsX4) in the nuclear receptor-binding SET domain protein 1 ( NSD1 ; MIM 606681) gene (related to Sotos syndrome), which was not associated with ataxia and is not related to the patient's phenotype. Sanger sequencing of NSD1 in two different laboratories confirmed the variant. Conclusions: NGS findings generally offer valuable information that can be used for clinical decision-making. However, an incidental finding that leads to defining new clinical and bioethical actions is also possible. Consequently, the biological importance of this type of genetic "incidentalome" must be determined.

Incidentalome in Neurogenetics: Pathogenic Variant of NSD1 in a Patient With Spinocerebellar Ataxia (SCA

Directory of Open Access Journals (Sweden)

Harvy Velasco

2018-03-01

Full Text Available Background: Genetic studies of late-onset sporadic ataxias (>40 years of age are not routinely indicated. For unresolved cases, next-generation sequencing (NGS tools, such as whole-exome sequencing (WES, are available for a definitive diagnosis.Case presentation: Our patient is a woman with a usual facial phenotype and anthropometry, who developed ataxia at 45 years of age, with no relevant family history and an initial clinical approach that ruled out common aetiologies. WES was performed when the patient was 54 years old. The results identified the heterozygous pathogenic variant c.248delA (p.N83MfsX4 in the nuclear receptor-binding SET domain protein 1 (NSD1; MIM 606681 gene (related to Sotos syndrome, which was not associated with ataxia and is not related to the patient's phenotype. Sanger sequencing of NSD1 in two different laboratories confirmed the variant.Conclusions: NGS findings generally offer valuable information that can be used for clinical decision-making. However, an incidental finding that leads to defining new clinical and bioethical actions is also possible. Consequently, the biological importance of this type of genetic “incidentalome” must be determined.

Bankruptcy and Voluntary Liquidation: Evidence for New Firms in East and West Germany after Unification

OpenAIRE

Prantl, Susanne

2003-01-01

Exploiting the unique economic situation after German unification, I investigate how exit decisions deviate between new firms in a transition and a comparatively stable market environment. Two competing exit mechanisms are considered: entrepreneurial self-selection via voluntary liquidation and external selection based on insolvency regulation. Distinguishing between the competing exit modes proves to be crucial in semi-parametric propor- tional hazard-rate estimations. Comparing East and Wes...

Proceedings of the Annual Meeting (14th) Aquatic Plant Control Research Planning and Operations Review, Held at Lake Eufaula, Oklahoma on 26-29 November 1979.

Science.gov (United States)

1980-10-01

Jr ... 76 ’- CHEMICAL CONTROL TECHNOLOGY DEVELOPMENT An Overview by Howard E. Westerdahl ..........--.-. 78 Development of Controlled-Release Herbicide...Experiment Station P. 0. Box 631 Vicksburg, MS 39180 Howard Westerdahl USAE Waterways Experiment Station P. 0. Box 631 Vicksburg, MS 39180 Kin Whittington...Ballroom 8:00 a.m. Chemical Control Technology Development - H. E. Westerdahl , WES, presiding 8:10 a.m. The Development of Controlled-Release

Water-enhanced solvation of organics

Energy Technology Data Exchange (ETDEWEB)

Lee, Jane H. [Univ. of California, Berkeley, CA (United States)

1993-07-01

Water-enhanced solvation (WES) was explored for Lewis acid solutes in Lewis base organic solvents, to develop cheap extract regeneration processes. WES for solid solutes was determined from ratios of solubilities of solutes in water-sat. and low-water solvent; both were determined from solid-liquid equilibrium. Vapor-headspace analysis was used to determine solute activity coefficients as function of organic phase water concentration. WES magnitudes of volatile solutes were normalized, set equal to slope of log γ_s vs x_w/x_s curve. From graph shape Δ(log γ_s) represents relative change in solute activity coefficient. Solutes investigated by vapor-headspace analysis were acetic acid, propionic acid, ethanol, 1,2-propylene glycol, 2,3-butylene glycol. Monocarboxylic acids had largest decrease in activity coefficient with water addition followed by glycols and alcohols. Propionic acid in cyclohexanone showed greatest water-enhancement Δ(log γ_acid)/Δ(x_w/x_acid) = -0.25. In methylcyclohexanone, the decrease of the activity coefficient of propionic acid was -0.19. Activity coefficient of propionic acid in methylcyclohexanone stopped decreasing once the water reached a 2:1 water to acid mole ratio, implying a stoichiometric relation between water, ketone, and acid. Except for 2,3-butanediol, activity coefficients of the solutes studied decreased monotonically with water content. Activity coefficient curves of ethanol, 1,2-propanediol and 2,3-butanediol did not level off at large water/solute mole ratio. Solutes investigated by solid-liquid equilibrium were citric acid, gallic acid, phenol, xylenols, 2-naphthol. Saturation concentration of citric acid in anhydrous butyl acetate increased from 0.0009 to 0.087 mol/L after 1.3 % (g/g) water co-dissolved into organic phase. Effect of water-enhanced solvation for citric acid is very large but very small for phenol and its derivatives.

Esthetic assessment of immediately restored implants combined with GBR and free connective tissue graft.

Science.gov (United States)

Kolerman, Roni; Nissan, Joseph; Mijiritsky, Eitan; Hamoudi, Nasreen; Mangano, Carlo; Tal, Haim

2016-11-01

Esthetic assessment of immediately restored implants combined with GBR and free connective tissue (CT) graft METHODS: A case-control, retrospective study involving 34 patients treated with maxillary anterior single implants, immediately placed and restored. Clinical and esthetic results were analyzed using standard clinical examination and a comprehensive index, comprising pink esthetic and white esthetic scores (PES/WES). The height of the implant crown and the corresponding height of the contralateral tooth crown were measured to identify mucosal recessions. The distance from the mucosal margin to the implant shoulder (DIM) was measured on the master model. Thirty of 34 implants fulfilled the strict success criteria set for dental implants with regard to osseointegration. Success was defined as implants with bone loss not exceeding 1.5 mm during the first year and loosing not more than 0.2 for each successive year. The other four implants were stable but did not meet the bone loss criteria mentioned above and defined as survived implants. Mean PES/WES was 14.44 ± 2.34 (range: 9-20). Mean PES was 7.12 ± 1.89 (range: 1-10). The highest mean values were achieved for the variable of root convexity/soft tissue color and texture (1.71 ± 0.46) whereas the mesial papilla (1.09 ± 0.62) proved to be the least pleasing. The mean WES was 7.32 ± 1.25 (range: 5-10). The difference between IC and contralateral TC was 0.54 mm. The mean value for the facial DIM was 3.82 ± 0.87 mm. An evaluation of soft and hard tissue augmentation in immediately restored immediate implant procedures was employed to obtain stable hard and soft tissues. The combined GBR and CT graft procedure achieved favorable peri-implant soft tissue condition and esthetic results. However, recession and incomplete papillas were frequently observed. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Xenograft tumors derived from malignant pleural effusion of the patients with non-small-cell lung cancer as models to explore drug resistance.

Science.gov (United States)

Xu, Yunhua; Zhang, Feifei; Pan, Xiaoqing; Wang, Guan; Zhu, Lei; Zhang, Jie; Wen, Danyi; Lu, Shun

2018-05-09

Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions show dramatic responses to specific tyrosine kinase inhibitors (TKIs); however, after 10-12 months, secondary mutations arise that confer resistance. We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK- and EGFR-targeted TKIs crizotinib and osimertinib, respectively. Genotypes of patient biopsies and xenograft tumors were determined by whole exome sequencing (WES), and patients and xenograft-bearing mice received targeted treatment (crizotinib or osimertinib) accordingly. Xenograft mice were also treated for prolonged periods to identify whether the development of drug resistance and/or treatment responses were associated with tumor size. Finally, the pathology of patients biopsies and xenograft tumors were compared histologically. The histological characteristics and chemotherapy responses of xenograft tumors were similar to the actual patients. WES showed that the genotypes of the xenograft and patient tumors were similar (an echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) gene fusion (patient/xenograft: CTC15035 EML4-ALK ) and EGFR L858R and T790M mutations (patient/xenograft: CTC15063 EGFR L858R, T790M )). After continuous crizotinib or osimertinib treatment, WES data suggested that acquired ALK E1210K mutation conferred crizotinib resistance in the CTC15035 EML4-ALK xenograft, while decreased frequencies of EGFR L858R and T790M mutations plus the appearance of v-RAF murine sarcoma viral oncogene homolog B (BRAF) G7V mutations and phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha (PIK3C2A) A86fs frame shift mutations led to osimertinib resistance in the CTC15063 EGFR L858R, T790M xenografts. We successfully developed a new method of generating

La función de las imágenes en la reflexión filosófica de Cicerón

Directory of Open Access Journals (Sweden)

Diony González

2012-12-01

Full Text Available The Greek rhetorical tradition and its development during the Hellenistic period allowed rhetoric in Rome to have a broader purpose, ceasing to be the source of creation of technical manuals with function and utility for a particular forensic activity. Cicero and, subsequently, Quintilian wrote a series of handbooks, rhetorical treatises, or literary dialogues with the purpose of establishing a complete theory of the new symbolic, political and persuasive role of the orator, not only through the creation of new rhetorical theories, but also of new frameworks for philosophical thought. This is the moment when rhetorical theory conceives the word as an image, and it is only through the process of representation that one can understand and construct a discourse about reality.

A Case of Miller Fisher Syndrome, Thromboembolic Disease, and Angioedema: Association or Coincidence?

OpenAIRE

Salehi, Nooshin; Choi, Eric D.; Garrison, Roger C.

2017-01-01

Patient: Male, 32 Final Diagnosis: Miller Fisher syndrome Symptoms: Ataxia ? headache ? ophthalmoplegia Medication: ? Clinical Procedure: Plasmapheresis Specialty: Neurology Objective: Rare co-existance of disease or pathology Background: Miller Fisher Syndrome is characterized by the clinical triad of ophthalmoplegia, ataxia, and areflexia, and is considered to be a variant of Guillain-Barre Syndrome. Miller Fisher Syndrome is observed in approximately 1?5% of all Guillain-Barre cases in Wes...

A novel AP4M1 mutation in autosomal recessive cerebral palsy syndrome and clinical expansion of AP-4 deficiency

OpenAIRE

Jameel, Muhammad; Klar, Joakim; Tariq, Muhammad; Moawia, Abubakar; Altaf Malik, Naveed; Seema Waseem, Syeda; Abdullah, Uzma; Naeem Khan, Tahir; Raininko, Raili; Baig, Shahid Mahmood; Dahl, Niklas

2014-01-01

BACKGROUND: Cerebral palsy (CP) is a heterogeneous neurodevelopmental disorder associated with intellectual disability in one-third of cases. Recent findings support Mendelian inheritance in subgroups of patients with the disease. The purpose of this study was to identify a novel genetic cause of paraplegic CP with intellectual disability in a consanguineous Pakistani family. METHODS: We performed whole-exome sequencing (WES) in two brothers with CP and intellectual disability. Analysis of AP...

Comparison of Hydraulic Conductivity Determinations in Co-located Conventional and Direct-Push Monitoring Wells

Science.gov (United States)

2011-03-08

and Development Center (ERDC) provided the funding for this project. We wish to thank our project monitors Tony Bednar (ERDC Environmental Laboratory...method for field determination of hy- draulic conductivity at contaminated sites (Butler 1997; Henebry and Robbins 2000; Bartlett et al. 2004). For a...ASTM International. www.astm.org Bartlett, Stephen A., Gary A. Robbins , J. Douglas Mandrick, Michael Barcelona, Wes McCall, and Mark Kram. 2004

Optimizing the Cost Effectiveness of Military Corrections; An Assessment of Program Evaluations and Related Data.

Science.gov (United States)

1978-06-09

of ex post facto researc h wes determined appropriate. Such research may be defined as systematic inqui ry in which the researcher lacks direct control...secondary , yet crit ical , part of the researc h wee based on unstructured observations of the military corrections system (while the researcher ‘ms...employment potential. Typically young • unskilled, aid poorly educated, the average offender (civilian or ailit&zy) has few marketable capabilities

Pipeline Optimization Program (PLOP)

Science.gov (United States)

2006-08-01

the framework of the Dredging Operations Decision Support System (DODSS, https://dodss.wes.army.mil/wiki/0). PLOP compiles industry standards and...efficiency point ( BEP ). In the interest of acceptable wear rate on the pump, industrial standards dictate that the flow Figure 2. Pump class as a function of...percentage of the flow rate corresponding to the BEP . Pump Acceptability Rules. The facts for pump performance, industrial standards and pipeline and

Research and Development in the U.S. Army Corps of Engineers: Improving the Common Stock of Knowledge

Science.gov (United States)

2011-08-01

cloth-covered frames with metal pipes to appear as muzzles. Others were wooden, fiber -board, paper, or cardboard panels that unfolded like a box... basalt from the Napa Valley in California. The WES Mobility Research Branch, in turn, sub- jected the materials to tests typical of conventional...In the concrete area, it de- veloped Portland cement reinforced with steel fibers to increase tensile strength, created foam- based concretes to resist

Assessment of groundwater vulnerability to contamination in Irbid govern orate, the north of Jordan

International Nuclear Information System (INIS)

Nawafleh, A.; Awawdeh, M.; Salameh, E.

2011-01-01

The main aquifers in northern Jordan showed little signs of contamination when modeled by the DRASTIC method, mainly due to topography and an invariably deep water table. Most of A7/B2 and B4/B5 aquifers are classified with low vulnerability and small regions classified as moderately vulnerable (0.20% and 0.80% respectivily). The dominance of low vulnerability in the study area is mainly attributed to the fact than DRASTIC assumes a very low vulnerability (rating value = 1) when water depths are greater than 30 m. Additionaly, DRASTIC does not demonstrate the capacity of satisfactorily outlining karst morphology. Both map removal and single-parameter sensitivity anayers showed that depth to water table and topography are the most decisive parameters in deteermining aquifer vulnerability. Net recharge, hydraulic conductivity, topography and depth to water table contribute significantly to the variation of the vulnerability index across the study area with the variation index being 75%. 71.5%. 66% and 63% respectively. These are higher than the theoretical topography have effective weights of 34%. 26% and 24%. respectively. These are higher than the theoretical weights assigned by the model (13%. 21.7% and 4.3% respectively). Wel AD1296 and spring AD0654 are the most contaminated water resources. The former is located within the vicinity of the Ramtha wastewater treatment plan and the latter is located within areas of agricultural activities and intensive cesspool usage. DRASTIC did not accurately predict the high concentrations of some chemicals, which highlight the need for new research into procedures for parmeter quantification and weighting. further investigations are also required in order to understand the mechanisms of groundwater recharge and contaminant transport in such aquifers. (authors).

A comprehensive characterization of rare mitochondrial DNA variants in neuroblastoma.

Science.gov (United States)

Calabrese, Francesco Maria; Clima, Rosanna; Pignataro, Piero; Lasorsa, Vito Alessandro; Hogarty, Michael D; Castellano, Aurora; Conte, Massimo; Tonini, Gian Paolo; Iolascon, Achille; Gasparre, Giuseppe; Capasso, Mario

2016-08-02

Neuroblastoma, a tumor of the developing sympathetic nervous system, is a common childhood neoplasm that is often lethal. Mitochondrial DNA (mtDNA) mutations have been found in most tumors including neuroblastoma. We extracted mtDNA data from a cohort of neuroblastoma samples that had undergone Whole Exome Sequencing (WES) and also used snap-frozen samples in which mtDNA was entirely sequenced by Sanger technology. We next undertook the challenge of determining those mutations that are relevant to, or arisen during tumor development. The bioinformatics pipeline used to extract mitochondrial variants from matched tumor/blood samples was enriched by a set of filters inclusive of heteroplasmic fraction, nucleotide variability, and in silico prediction of pathogenicity. Our in silico multistep workflow applied both on WES and Sanger-sequenced neuroblastoma samples, allowed us to identify a limited burden of somatic and germline mitochondrial mutations with a potential pathogenic impact. The few singleton germline and somatic mitochondrial mutations emerged, according to our in silico analysis, do not appear to impact on the development of neuroblastoma. Our findings are consistent with the hypothesis that most mitochondrial somatic mutations can be considered as 'passengers' and consequently have no discernible effect in this type of cancer.

A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic adenoid cystic carcinoma.

Science.gov (United States)

Goncalves, Priscila H; Heilbrun, Lance K; Barrett, Michael T; Kummar, Shivaani; Hansen, Aaron R; Siu, Lillian L; Piekarz, Richard L; Sukari, Ammar W; Chao, Joseph; Pilat, Mary Jo; Smith, Daryn W; Casetta, Lindsay; Boerner, Scott A; Chen, Alice; Lenkiewicz, Elizabeth; Malasi, Smriti; LoRusso, Patricia M

2017-05-16

Vorinostat is a histone deacetylase inhibitor (HDACi). Based on a confirmed partial response (PR) in an adenoid cystic carcinoma (ACC) patient treated with vorinostat in a prior phase 1 trial, we initiated this phase 2 trial. Vorinostat was administered orally 400 mg daily, 28 day cycles. The primary objective was to evaluate response rate (RR). Exploratory studies included whole exome sequencing (WES) of selected patients. Thirty patients were enrolled. Median age of patients was 53 years (range 21-73). Median number of cycles was 5 (range 1-66). Lymphopenia (n = 5), hypertension (n = 3), oral pain (n = 2), thromboembolic events (n = 2) and fatigue (n = 2) were the only grade 3 adverse events (AEs) that occurred in more than 1 patient. Eleven patients were dose reduced secondary to drug-related AEs. Two patients had a partial response (PR), with response durations of 53 and 7.2 months. One patient had a minor response with a decrease in ascites (for 19 cycles). Stable disease was the best response in 27 patients. Targeted and WES of 8 patients in this trial identified mutations in chromatin remodeling genes highlighting the role of the epigenome in ACC. Vorinostat demonstrated efficacy in patients with ACC supporting the inclusion of HDACi in future studies to treat ACC.

Eloqüência, liberdade e educação no Dialogus de oratoribus

Directory of Open Access Journals (Sweden)

Ariovaldo A. Peterlini

2006-07-01

Full Text Available Visa o trabalho trazer à consideração de hoje idéias e fatos selecionados no Dialogus de oratoribus, de Tácito, como auxílio ao melhor entendimento do signi?cado da maior ou menor liberdade de ser e expressar-se, consoante o sistema político e o educacional, bem como da atuação da eloqüência nessa liberdade. A oratória tida por decadente na época de Tácito, embora vista ainda como arte de proteção e salvação é raramente, quase a medo, tratada à luz da política dominante. A educação falha e a “paz” política seriam as causas dessa decadência na época imperial. Na visão romana, a liberdade propriamente dita, a absoluta libertas, depende inicialmente dos educadores. A liberdade está também condicionada ao grau de conhecimento, em cuja área a persuasão “democrática” da eloqüência pode licitamente agir, e a uma política capaz de respeitar essa liberdade. No Império, a eloqüência não se suicidaria, ousando contra o príncipe. Daí que, no dizer de Syme, a oratória que sobrevivia então era o “modelo da eloqüência forense dos acusadores, aquela eloqüência que jorrava sangue e tresandava a ganhos ilícitos”. As escolas tinham nisso parte grande, em virtude da super?cialidade da educação na época. Tendo vivido e vivendo sob a pressão dos imperadores, embora deixe entrever sua angústia, Tácito acomoda-se para sobreviver, mas descobre uma maneira de ensinar a verdade, narrando o que aconteceu no passado, porque a maior parte das pessoas aprende com o que acontece aos outros (plures aliorum euentis docentur.

Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech

OpenAIRE

Worthey, Elizabeth A; Raca, Gordana; Laffin, Jennifer J; Wilk, Brandon M; Harris, Jeremy M; Jakielski, Kathy J; Dimmock, David P; Strand, Edythe A; Shriberg, Lawrence D

2013-01-01

Background Childhood apraxia of speech (CAS) is a rare, severe, persistent pediatric motor speech disorder with associated deficits in sensorimotor, cognitive, language, learning and affective processes. Among other neurogenetic origins, CAS is the disorder segregating with a mutation in FOXP2 in a widely studied, multigenerational London family. We report the first whole-exome sequencing (WES) findings from a cohort of 10 unrelated participants, ages 3 to 19 years, with well-characterized CA...

Work-Family Balancing and Working Time: What Measures are Available to Canadian Workers and What Measures should Employers Develop?

OpenAIRE

Diane-Gabrielle Tremblay; Elmustapha Najem; Renaud Paquet

2007-01-01

This article examines work-family balance. Data from the Workplace and Employee Survey (WES) was used to assess the overall situation of this phenomenon in Canada. Representative statistical data was used to determine to what extent employers have taken the work-family challenge into account. Our data indicate that the progress observed regarding the social debate on work-family balance has not necessarily translated into a marked improvement in facilitating conditions in workplaces and that ...

Proceedings of the Annual Meeting (21st), Aquatic Plant Control Research Program Held in Mobile, Alabama on 17-21 November 1986

Science.gov (United States)

1987-11-01

E. Westerdahl , WES, Presiding 8:15 a.m. Aquatic Herbicide User Guide Herbicide Concentration/Exposure Time Relationships-2,4-D, Sonar, Endothall, and...Diquat -H. E. Westerdahl 8:30 a.m. Controlled-Release Poly GMA/2,4-D Evaluation -R. Gupta, Day Chem, Inc., Dayton, Ohio 8:45 a.m. Herbicide/Adjuvant...0631 USAE Waterways Experiment Howard Westerdahl Station, PO Box 631 USAE Waterways Experiment Vicksburg, MS 39180-0631 Station, PO Box 631 Michael

Evaluation of Upland Disposal of Oakland Harbor, California, Sediment. Volume 2: Inner and Outer Harbor Sediments

Science.gov (United States)

1993-08-01

the drop size and terminal velocities of natural rain- fall, factors which are critical in erosion and infiltration studies ( Westerdahl and Skogerboe... Westerdahl and Skogerboe 1982; Lee and Skogerboe 1984; Skogerboe et al. 1987). The WES Rainfall Simulator/ Lysimeter System proved to be an effective...Waters (Phase IIIA of -42-Foot Project); Volume 2: Appendixes," iNL-83-2, Vol 2, Battelle/Marine Science Laboratory, Sequim, WA. Westerdahl , H. E., and

Automation of Military Civil Engineering and Site Design Functions: Software Evaluation

Science.gov (United States)

1989-09-01

AutoCad , in-house application programs written in AutoCad command language, AutoLISP , and BASIC Would like to obtain: Surveying, earthwork, utilities...Experiment Station (WES) Corps library programs, no one software is being used more than another. For drafting, AutoCAD has been the most commonly...ware packages evaluated. D.C.A. Engineering Software D.C.A. software is used to enhance the AutoCAD drafting package and operates solely within the

Exome sequencing identifies pathogenic variants of VPS13B in a patient with familial 16p11.2 duplication

OpenAIRE

Dastan, Jila; Chijiwa, Chieko; Tang, Flamingo; Martell, Sally; Qiao, Ying; Rajcan-Separovic, Evica; Lewis, M. E. Suzanne

2016-01-01

Background The recurrent microduplication of 16p11.2 (dup16p11.2) is associated with a broad spectrum of neurodevelopmental disorders (NDD) confounded by incomplete penetrance and variable expressivity. This inter- and intra-familial clinical variability highlights the importance of personalized genetic counselling in individuals at-risk. Case presentation In this study, we performed whole exome sequencing (WES) to look for other genomic alterations that could explain the clinical variability...

The Baltimore Engineers and the Chesapeake Bay, 1961-1987

Science.gov (United States)

1988-01-01

Army Engineer Waterways Experiment Station: David F. Bastian and Norman W. Scheffner. At the University of Maryland Baltimore County: Howard E...Howard, Smallwood and Armisted. By the time of the Civil War, Baltimore was one of the best defended ports in the world. The forts at Hampton Roads and...Marine Sciences. The salinity and current velocity data were collected at 199 and 205 stations respectively. Norman Scheffner of WES de- veloped a

Concrete and Rock Tests, Major Rehabilitation of Dresden Island Lock and Dam, Illinois Waterway, Chicago District. Phase II. Compliance, Scour Detection.

Science.gov (United States)

1981-03-01

uwniin SHUAR STMSS AREA ________________________ URINO NO. GW-5 S AMPLE NO. DEPTH 33 OIRECT SHEAR TEST REPORT (ROCK) WES AR11490 EDITION oP JUNf4 SIs...28 " 24 -T2. 70 ILVAMO DRESDEN ISWIDM W)C AND DAM ANA *am* M E-1 ~N L15 .4-15.9/494.1-494.6 IDM2" FB7 NVJG WUCT SHUAR TT ROem -񓡌 (IM 10 1" IO-j Ml

Environmental Management Systems in Local Authorities: The Case Study of the Cesana Torinese Municipality, a Turin 2006 Olympic Site

OpenAIRE

Serena Botta; Claudio Comoglio

2007-01-01

Environmental certification according to the ISO 14001 standard and EMAS regulation represents an efficient tool for those organizations who want to continuously improve their environmental performances. Even though first thought up for application to the industrial section, in recent years these schemes have also proved to be valid in organizations with territorial competences, such as local authorities. The case study of the Cesana Torinese municipality, an important ski resort in North Wes...

FABLES IN THE AGORA: FROM ARISTOTLE TO THE CENTURY OF ENLIGHTENMENT

Directory of Open Access Journals (Sweden)

Márcia Seabra Neves

2013-12-01

Full Text Available Having been long established in western poetic tradition as a short composition of ethical intent, usually performed by anthropomorphized animals and conveying a rule of behavior, the fable has represented, ever since its origins, a key strategy of persuasion at the service of orators seeking to convince and influence an audience. Originally defined as a rhetorical genre and inevitably mirroring social and historical mutations, the fable as well as the moralities inferred from it have played varying functions and accomplished different goals in the course of centuries, so as to accommodate changing communicative needs. In this article, we seek to provide a critical and diachronic survey of the resonance of classical rhetoric in the definition of fable as a genre and examine its literary manifestations from Aristotle to the Enlightenment.

Optimal Wind Energy Integration in Large-Scale Electric Grids

Science.gov (United States)

Albaijat, Mohammad H.

profit for investors for renting their transmission capacity, and cheaper electricity for end users. We propose a hybrid method based on a heuristic and deterministic method to attain new transmission lines additions and increase transmission capacity. Renewable energy resources (RES) have zero operating cost, which makes them very attractive for generation companies and market participants. In addition, RES have zero carbon emission, which helps relieve the concerns of environmental impacts of electric generation resources' carbon emission. RES are wind, solar, hydro, biomass, and geothermal. By 2030, the expectation is that more than 30% of electricity in the U.S. will come from RES. One major contributor of RES generation will be from wind energy resources (WES). Furthermore, WES will be an important component of the future generation portfolio. However, the nature of WES is that it experiences a high intermittency and volatility. Because of the great expectation of high WES penetration and the nature of such resources, researchers focus on studying the effects of such resources on the electric grid operation and its adequacy from different aspects. Additionally, current market operations of electric grids add another complication to consider while integrating RES (e.g., specifically WES). Mandates by market rules and long-term analysis of renewable penetration in large-scale electric grid are also the focus of researchers in recent years. We advocate a method for high-wind resources penetration study on large-scale electric grid operations. PMU is a geographical positioning system (GPS) based device, which provides immediate and precise measurements of voltage angle in a high-voltage transmission system. PMUs can update the status of a transmission line and related measurements (e.g., voltage magnitude and voltage phase angle) more frequently. Every second, a PMU can provide 30 samples of measurements compared to traditional systems (e.g., supervisory control and

[Reconstruction assisted by 3D printing in maxillofacial surgery].

Science.gov (United States)

Ernoult, C; Bouletreau, P; Meyer, C; Aubry, S; Breton, P; Bachelet, J-T

2015-04-01

3-dimensional models (3D) appeared in the medical field 20 years ago. The recent development of consumer 3D printers explains the renewed interest in this technology. We describe the technical and practical modalities of this surgical tool, illustrated by concrete examples. The OsiriX(®) software (version 5.8.5, Geneva, Switzerland) was used for 3D surface reconstruction of the area of interest, the generation and export of ".stl" file. The NetFabb(®) software (Basic version 5.1.1, Lupburg, Germany) provided the preparation of ".stl" file. The 3D-printer was an Up plus 2 Easy 120(®) (PP3DP, Beijing Technology Co. TierTime Ltd., Chine). The printer used fused deposition modeling. The softwar Up!(®) allowed the 3d impression as required. The first case illustrated the value of 3D printing in the upper (frontal sinus and orbital roof). The second case concerned the preconfiguration of the osteosynthesis material for a complex fracture of the midface through the "mirroring" system. The third case showed the conformation of a prereconstruction for segmental mandibulectomy. Current 3D-printers are easy to use and represent a promising solution for medical prototyping. The 3D printing will quickly become undeniable because of its advantages: information sharing, simulation, surgical guides, pedagogy. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Identification of a conserved protein involved in anaerobic unsaturated fatty acid synthesis in Neiserria gonorrhoeae: implications for facultative and obligate anaerobes that lack FabA

Science.gov (United States)

Isabella, Vincent M.; Clark, Virginia L.

2011-01-01

SUMMARY Transcriptome analysis of the facultative anaerobe, Neisseria gonorrhoeae, revealed that many genes of unknown function were induced under anaerobic conditions. Mutation of one such gene, NGO1024, encoding a protein belonging to the 2-nitropropane dioxygenase-like superfamiliy of proteins, was found to result in an inability of gonococci to grow anaerobically. Anaerobic growth of an NG1024 mutant was restored upon supplementation with unsaturated fatty acids (UFA), but not with the saturated fatty acid palmitate. Gonococcal fatty acid profiles confirmed that NGO1024 was involved in UFA synthesis anaerobically, but not aerobically, demonstrating that gonococci contain two distinct pathways for the production of UFAs, with a yet unidentified aerobic mechanism, and an anaerobic mechanism involving NGO1024. Expression of genes involved in classical anaerobic UFA synthesis, fabA, fabM, and fabB, was toxic in gonococci and unable to complement a NGO1024 mutation, suggesting that the chemistry involved in gonococcal anaerobic UFA synthesis is distinct from that of the classical pathway. NGO1024 homologs, which we suggest naming UfaA, form a distinct lineage within the 2-nitropropane dioxygenase-like superfamily, and are found in many facultative and obligate anaerobes that produce UFAs but lack fabA, suggesting that UfaA is part of a widespread pathway involved in UFA synthesis. PMID:21895795

Whole-exome sequencing identifies novel compound heterozygous mutations in USH2A in Spanish patients with autosomal recessive retinitis pigmentosa.

Science.gov (United States)

Méndez-Vidal, Cristina; González-Del Pozo, María; Vela-Boza, Alicia; Santoyo-López, Javier; López-Domingo, Francisco J; Vázquez-Marouschek, Carmen; Dopazo, Joaquin; Borrego, Salud; Antiñolo, Guillermo

2013-01-01

Retinitis pigmentosa (RP) is an inherited retinal dystrophy characterized by extreme genetic and clinical heterogeneity. Thus, the diagnosis is not always easily performed due to phenotypic and genetic overlap. Current clinical practices have focused on the systematic evaluation of a set of known genes for each phenotype, but this approach may fail in patients with inaccurate diagnosis or infrequent genetic cause. In the present study, we investigated the genetic cause of autosomal recessive RP (arRP) in a Spanish family in which the causal mutation has not yet been identified with primer extension technology and resequencing. We designed a whole-exome sequencing (WES)-based approach using NimbleGen SeqCap EZ Exome V3 sample preparation kit and the SOLiD 5500×l next-generation sequencing platform. We sequenced the exomes of both unaffected parents and two affected siblings. Exome analysis resulted in the identification of 43,204 variants in the index patient. All variants passing filter criteria were validated with Sanger sequencing to confirm familial segregation and absence in the control population. In silico prediction tools were used to determine mutational impact on protein function and the structure of the identified variants. Novel Usher syndrome type 2A (USH2A) compound heterozygous mutations, c.4325T>C (p.F1442S) and c.15188T>G (p.L5063R), located in exons 20 and 70, respectively, were identified as probable causative mutations for RP in this family. Family segregation of the variants showed the presence of both mutations in all affected members and in two siblings who were apparently asymptomatic at the time of family ascertainment. Clinical reassessment confirmed the diagnosis of RP in these patients. Using WES, we identified two heterozygous novel mutations in USH2A as the most likely disease-causing variants in a Spanish family diagnosed with arRP in which the cause of the disease had not yet been identified with commonly used techniques. Our data

Characterization of the env gene and long terminal repeat of molecularly cloned Friend mink cell focus-inducing virus DNA.

OpenAIRE

Adachi, A; Sakai, K; Kitamura, N; Nakanishi, S; Niwa, O; Matsuyama, M; Ishimoto, A

1984-01-01

The highly oncogenic erythroleukemia-inducing Friend mink cell focus-inducing (MCF) virus was molecularly cloned in phage lambda gtWES.lambda B, and the DNA sequences of the env gene and the long terminal repeat were determined. The nucleotide sequences of Friend MCF virus and Friend spleen focus-forming virus were quite homologous, supporting the hypothesis that Friend spleen focus-forming virus might be generated via Friend MCF virus from an ecotropic Friend virus mainly by some deletions. ...

Identification of Heterozygous Single- and Multi-exon Deletions in IL7R by Whole Exome Sequencing.

OpenAIRE

Engelhardt, Karin R; Xu, Yaobo; Grainger, Angela; Germani Batacchi, Mila G C; Swan, David J; Willet, Joseph D P; Abd Hamid, Intan J; Agyeman, Philipp; Barge, Dawn; Bibi, Shahnaz; Jenkins, Lucy; Flood, Terence J; Abinun, Mario; Slatter, Mary A; Gennery, Andrew R

2017-01-01

Purpose We aimed to achieve a retrospective molecular diagnosis by applying state-of-the-art genomic sequencing methods to past patients with T-B+NK+ severe combined immunodeficiency (SCID). We included identification of copy number variations (CNVs) by whole exome sequencing (WES) using the CNV calling method ExomeDepth to detect gene alterations for which routine Sanger sequencing analysis is not suitable, such as large heterozygous deletions. Methods Of a total of 12 undiagnosed patients w...

Contextual factors, methodological principles and teacher cognition

OpenAIRE

Walsh, Rupert; Wyatt, Mark

2014-01-01

Teachers in various contexts worldwide are sometimes unfairly criticized for not putting teaching methods developed for the well-resourced classrooms of Western countries into practice. Factors such as the teachers’ “misconceptualizations” of “imported” methods, including Communicative Language Teaching (CLT), are often blamed, though the challenges imposed by “contextual demands,” such as large class sizes, are sometimes recognised. Meanwhile, there is sometimes an assumption that in the Wes...

The Effect of Channa striatus (Haruan Extract on Pain and Wound Healing of Post-Lower Segment Caesarean Section Women

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Siti Zubaidah Ab Wahab

2015-01-01

Full Text Available Channa striatus has been consumed for decades as a remedy to promote wound healing by women during postpartum period. The objectives of this study were to compare postoperative pain, wound healing based on wound evaluation scale (WES, wound cosmetic appearance based on visual analogue scale (VAS scores and patient satisfaction score (PSS, and safety profiles between C. striatus group and placebo group after six weeks of lower segment caesarean section (LSCS delivery. A randomised, double-blind, placebo-controlled study was conducted. Subjects were randomised in a ratio of 1 : 1 into either the C. striatus group (500 mg daily or placebo group (500 mg of maltodextrin daily. 76 subjects were successfully randomised, with 38 in the C. striatus group and 35 in the placebo group. There were no significant differences in postoperative pain p=0.814 and WES p=0.160 between the C. striatus and placebo groups. However, VAS and PSS in the C. striatus group were significantly better compared with the placebo group (p=0.014 and p<0.001, resp.. The safety profiles showed no significant differences between the groups. In conclusion, six-week supplementation of 500 mg of C. striatus extract showed marked differences in wound cosmetic appearance and patient’s satisfaction and is safe for human consumption.

Whole-Exome Sequencing Reveals Clinically Relevant Variants in Family Affected with Autism Spectrum Disorder

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Jiaxiu Zhou

2016-10-01

Full Text Available Chromosomal microarray (CMA has been suggested as a first tier clinical diagnostic test for ASD. High-throughput sequencing (HTS has associated hundreds of genes associated with ASD. Whole Exome Sequencing (WES was used in combination with CMA to identify clinically-relevant ASD variants. In prior work, a trio-based (father, mother, and proband WGS (Whole Genome Sequencing was used to reveal clinically-relevant de novo, or inherited, rare variants in half (16 / 32 of the ASD families in which all probands had normal, or VOUS (Variant of Uncertain Clinical Significance, CMA results. In this study, after CMA screening chromosome structural abnormalities of a proband affected with ASD, a WES was performed on the patient and parents. Some rare de novo, and inherited, variants were detected using trio-based bioinformatics analysis. ASD variants were ranked by SFARI Gene score, HPO (human phenotype ontology, protein function damage, and manual searching PubMed. Sanger sequencing was used to validated some candidate variants in family members. A de novo homozygous mutation in SPG11 (p.C209F, two inherited, compound-heterozygote mutations in SCN9A (p.Q10R and p.R1893H and BEST1 (p.A135V and p.A297V were confirmed. Heterozygous mutations in TSC1 (p.S487C and SHANK2 (p.Arg569His inherited from mother were also confirmed.

A Recurrent De Novo Variant in NACC1 Causes a Syndrome Characterized by Infantile Epilepsy, Cataracts, and Profound Developmental Delay.

Science.gov (United States)

Schoch, Kelly; Meng, Linyan; Szelinger, Szabolcs; Bearden, David R; Stray-Pedersen, Asbjorg; Busk, Oyvind L; Stong, Nicholas; Liston, Eriskay; Cohn, Ronald D; Scaglia, Fernando; Rosenfeld, Jill A; Tarpinian, Jennifer; Skraban, Cara M; Deardorff, Matthew A; Friedman, Jeremy N; Akdemir, Zeynep Coban; Walley, Nicole; Mikati, Mohamad A; Kranz, Peter G; Jasien, Joan; McConkie-Rosell, Allyn; McDonald, Marie; Wechsler, Stephanie Burns; Freemark, Michael; Kansagra, Sujay; Freedman, Sharon; Bali, Deeksha; Millan, Francisca; Bale, Sherri; Nelson, Stanley F; Lee, Hane; Dorrani, Naghmeh; Goldstein, David B; Xiao, Rui; Yang, Yaping; Posey, Jennifer E; Martinez-Agosto, Julian A; Lupski, James R; Wangler, Michael F; Shashi, Vandana

2017-02-02

Whole-exome sequencing (WES) has increasingly enabled new pathogenic gene variant identification for undiagnosed neurodevelopmental disorders and provided insights into both gene function and disease biology. Here, we describe seven children with a neurodevelopmental disorder characterized by microcephaly, profound developmental delays and/or intellectual disability, cataracts, severe epilepsy including infantile spasms, irritability, failure to thrive, and stereotypic hand movements. Brain imaging in these individuals reveals delay in myelination and cerebral atrophy. We observe an identical recurrent de novo heterozygous c.892C>T (p.Arg298Trp) variant in the nucleus accumbens associated 1 (NACC1) gene in seven affected individuals. One of the seven individuals is mosaic for this variant. NACC1 encodes a transcriptional repressor implicated in gene expression and has not previously been associated with germline disorders. The probability of finding the same missense NACC1 variant by chance in 7 out of 17,228 individuals who underwent WES for diagnoses of neurodevelopmental phenotypes is extremely small and achieves genome-wide significance (p = 1.25 × 10 -14 ). Selective constraint against missense variants in NACC1 makes this excess of an identical missense variant in all seven individuals more remarkable. Our findings are consistent with a germline recurrent mutational hotspot associated with an allele-specific neurodevelopmental phenotype in NACC1. Copyright © 2017 American Society of Human Genetics. All rights reserved.

1p13.2 deletion displays clinical features overlapping Noonan syndrome, likely related to NRAS gene haploinsufficiency

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Natália Duarte Linhares

Full Text Available Abstract Deletion-induced hemizygosity may unmask deleterious autosomal recessive variants and be a cause of the phenotypic variability observed in microdeletion syndromes. We performed complete exome sequencing (WES analysis to examine this possibility in a patient with 1p13.2 microdeletion. Since the patient displayed clinical features suggestive of Noonan Syndrome (NS, we also used WES to rule out the presence of pathogenic variants in any of the genes associated with the different types of NS. We concluded that the clinical findings could be attributed solely to the 1p13.2 haploinsufficiency. Retrospective analysis of other nine reported patients with 1p13.2 microdeletions showed that six of them also presented some characteristics of NS. In all these cases, the deleted segment included the NRAS gene. Gain-of-function mutations of NRAS gene are causally related to NS type 6. Thus, it is conceivable that NRAS haploinsufficiency and gain-of-function mutations may have similar clinical consequences. The same phenomenon has been described for two other genes belonging to the Ras/MAPK pathway: MAP2K2 and SHOC2. In conclusion, we here report genotype-phenotype correlations in patients with chromosome 1p13.2 microdeletions and we propose that NRAS may be a critical gene for the NS characteristics in the patients.

Identification of a novel missense mutation of MAF in a Japanese family with congenital cataract by whole exome sequencing: a clinical report and review of literature.

Science.gov (United States)

Narumi, Yoko; Nishina, Sachiko; Tokimitsu, Motoharu; Aoki, Yoko; Kosaki, Rika; Wakui, Keiko; Azuma, Noriyuki; Murata, Toshinori; Takada, Fumio; Fukushima, Yoshimitsu; Kosho, Tomoki

2014-05-01

Congenital cataracts are the most important cause of severe visual impairment in infants. Genetic factors contribute to the disease development and 29 genes are known to cause congenital cataracts. Identifying the genetic cause of congenital cataracts can be difficult because of genetic heterogeneity. V-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (MAF) encodes a basic region/leucine zipper transcription factor that plays a key role as a regulator of embryonic lens fiber cell development. MAF mutations have been reported to cause juvenile-onset pulverulent cataract, microcornea, iris coloboma, and other anterior segment dysgenesis. We report on six patients in a family who have congenital cataracts were identified MAF mutation by whole exome sequencing (WES). The heterozygous MAF mutation Q303L detected in the present family occurs in a well conserved glutamine residue at the basic region of the DNA-binding domain. All affected members showed congenital cataracts. Three of the six members showed microcornea and one showed iris coloboma. Congenital cataracts with MAF mutation exhibited phenotypically variable cataracts within the family. Review of the patients with MAF mutations supports the notion that congenital cataracts caused by MAF mutations could be accompanied by microcornea and/or iris coloboma. WES is a useful tool for detecting disease-causing mutations in patients with genetically heterogeneous conditions. © 2014 Wiley Periodicals, Inc.

Esthetic outcome and alterations of soft tissue around single implant crowns: a 2-year prospective study.

Science.gov (United States)

Gu, Ying-Xin; Shi, Jun-Yu; Zhuang, Long-Fei; Qiao, Shi-Chong; Xu, You-You; Lai, Hong-Chang

2015-08-01

The aim of this prospective study was to assess the esthetic outcome and alterations of peri-implant soft tissue using tissue-level implants. Furthermore, the influencing factors, including grafting and gingival biotype, of esthetic outcome of peri-implant soft tissue were also evaluated. Of 38 patients with single missing anterior tooth in maxilla were treated with a Straumann (®) Standard Plus SLA implant. Bone augmentation was performed in 24 patients. Follow-up was conducted at 12 and 24 months after definitive crowns placement. Esthetic outcome using the pink esthetic score/white esthetic score (PES/WES) and clinical parameters were evaluated. The mean PES/WES value at baseline, 1-year, and 2-year examination was 13.79, 14.87, and 14.96. Significant improvement was found between baseline and 1-year examination (P esthetic area. Favorable short-term esthetic outcome and stability of soft tissue around single implant crowns can be expected in patients with or without graft. However, graft procedures might have an unfavorable effect on the esthetic outcome. Gingival biotype can be considered as prognostic factor for esthetic outcome. RCTs with long-term follow-up are needed to provide evidence for the long-term stability of peri-implant soft tissue using tissue-level implant systems. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Biallelic loss-of-function variants in DOCK3 cause muscle hypotonia, ataxia, and intellectual disability.

Science.gov (United States)

Helbig, K L; Mroske, C; Moorthy, D; Sajan, S A; Velinov, M

2017-10-01

DOCK3 encodes the dedicator of cytokinesis 3 protein, a member of the DOCK180 family of proteins that are characterized by guanine-nucleotide exchange factor activity. DOCK3 is expressed exclusively in the central nervous system and plays an important role in axonal outgrowth and cytoskeleton reorganization. Dock3 knockout mice exhibit motor deficiencies with abnormal ataxic gait and impaired learning. We report 2 siblings with biallelic loss-of-function variants in DOCK3. Diagnostic whole-exome sequencing (WES) and chromosomal microarray were performed on a proband with severe developmental disability, hypotonia, and ataxic gait. Testing was also performed on the proband's similarly affected brother. A paternally inherited 458 kb deletion in chromosomal region 3p21.2 disrupting the DOCK3 gene was identified in both affected siblings. WES identified a nonsense variant c.382C>G (p.Gln128*) in the DOCK3 gene (NM_004947) on the maternal allele in both siblings. Common features in both affected individuals include severe developmental disability, ataxic gait, and severe hypotonia, which recapitulates the Dock3 knockout mouse phenotype. We show that complete DOCK3 deficiency in humans leads to developmental disability with significant hypotonia and gait ataxia, probably due to abnormal axonal development. © 2017 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Coffin-Siris syndrome with café-au-lait spots, obesity and hyperinsulinism caused by a mutation in the ARID1B gene.

Science.gov (United States)

Sonmez, Fatma Mujgan; Uctepe, Eyyup; Gunduz, Mehmet; Gormez, Zeliha; Erpolat, Seval; Oznur, Murat; Sagiroglu, Mahmut Samil; Demirci, Huseyin; Gunduz, Esra

2016-08-01

Coffin-Siris syndrome (CSS) (MIM 135900) is characterized by developmental delay, severe speech impairment, distinctive facial features, hypertrichosis, aplasia or hypoplasia of the distal phalanx or nail of the fifth digit and agenesis of the corpus callosum. Recently, it was shown that mutations in the ARID1B gene are the main cause of CSS, accounting for 76% of identified mutations. Here, we report a 15 year-old female patient who was admitted to our clinic with seizures, speech problems, dysmorphic features, bilaterally big, large thumb, café-au-lait (CAL) spots, obesity and hyperinsulinism. First, the patient was thought to have an association of neurofibromatosis and Rubinstein Taybi syndrome. Because of the large size of the NF1 gene for neurofibromatosis and CREBBP gene for Rubinstein Taybi syndrome, whole exome sequence analysis (WES) was conducted and a novel ARID1B mutation was identified. The proband WES test identified a novel heterozygous frameshift mutation c.3394_3395insTA in exon 13 of ARID1B (NM_017519.2) predicting a premature stop codon p.(Tyr1132Leufs*67). Sanger sequencing confirmed the heterozygous c.3394_3395insTA mutation in the proband and that it was not present in her parents indicating de novo mutation. Further investigation and new cases will help to understand this phenomenon better.

Novel Homozygous Missense Mutation in RYR1 Leads to Severe Congenital Ptosis, Ophthalmoplegia, and Scoliosis in the Absence of Myopathy.

Science.gov (United States)

Dilaver, Nafi; Mazaheri, Neda; Maroofian, Reza; Zeighami, Jawaher; Seifi, Tahere; Zamani, Mina; Sedaghat, Alireza; Shariati, Gholam Reza; Galehdari, Hamid

2017-12-01

Ryanodine receptor 1 ( RYR1 ) is an intracellular calcium receptor primarily expressed in skeletal muscle with a role in excitation contraction. Both dominant and recessive mutations in the RYR1 gene cause a range of RYR1 -related myopathies and/or susceptibility to malignant hyperthermia (MH). Recently, an atypical manifestation of ptosis, variably presenting with ophthalmoplegia, facial paralysis, and scoliosis but without significant muscle weakness, has been reported in 9 cases from 4 families with bialleic variants in RYR1 . Two affected children from a consanguineous family with severe congenital ptosis, ophthalmoplegia, scoliosis, and distinctive long faces but without skeletal myopathy were studied. To identify the cause of the hereditary condition, DNA from the proband was subjected to whole exome sequencing (WES). WES revealed a novel homozygous missense variant in RYR1 (c.14066T>A; p.IIe4689Asn), which segregated within the family. Although the phenotype of the affected siblings in this study was similar to previously described cases, the clinical features were more severely expressed. Our findings contribute to the expansion of phenotypes related to RYR1 dysfunction. Additionally, it supports a new RYR1 -related clinical presentation without musculoskeletal involvement. It is important that individuals with RYR1 mutations are considered susceptible to MH, as 70% of the MH cases are caused by mutations in the RYR1 gene.

Rare mutations and potentially damaging missense variants in genes encoding fibrillar collagens and proteins involved in their production are candidates for risk for preterm premature rupture of membranes.

Science.gov (United States)

Modi, Bhavi P; Teves, Maria E; Pearson, Laurel N; Parikh, Hardik I; Chaemsaithong, Piya; Sheth, Nihar U; York, Timothy P; Romero, Roberto; Strauss, Jerome F

2017-01-01

Preterm premature rupture of membranes (PPROM) is the leading identifiable cause of preterm birth with ~ 40% of preterm births being associated with PPROM and occurs in 1% - 2% of all pregnancies. We hypothesized that multiple rare variants in fetal genes involved in extracellular matrix synthesis would associate with PPROM, based on the assumption that impaired elaboration of matrix proteins would reduce fetal membrane tensile strength, predisposing to unscheduled rupture. We performed whole exome sequencing (WES) on neonatal DNA derived from pregnancies complicated by PPROM (49 cases) and healthy term deliveries (20 controls) to identify candidate mutations/variants. Genotyping for selected variants from the WES study was carried out on an additional 188 PPROM cases and 175 controls. All mothers were self-reported African Americans, and a panel of ancestry informative markers was used to control for genetic ancestry in all genetic association tests. In support of the primary hypothesis, a statistically significant genetic burden (all samples combined, SKAT-O p-value = 0.0225) of damaging/potentially damaging rare variants was identified in the genes of interest-fibrillar collagen genes, which contribute to fetal membrane strength and integrity. These findings suggest that the fetal contribution to PPROM is polygenic, and driven by an increased burden of rare variants that may also contribute to the disparities in rates of preterm birth among African Americans.

Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis.

Science.gov (United States)

Juge, Pierre-Antoine; Borie, Raphaël; Kannengiesser, Caroline; Gazal, Steven; Revy, Patrick; Wemeau-Stervinou, Lidwine; Debray, Marie-Pierre; Ottaviani, Sébastien; Marchand-Adam, Sylvain; Nathan, Nadia; Thabut, Gabriel; Richez, Christophe; Nunes, Hilario; Callebaut, Isabelle; Justet, Aurélien; Leulliot, Nicolas; Bonnefond, Amélie; Salgado, David; Richette, Pascal; Desvignes, Jean-Pierre; Lioté, Huguette; Froguel, Philippe; Allanore, Yannick; Sand, Olivier; Dromer, Claire; Flipo, René-Marc; Clément, Annick; Béroud, Christophe; Sibilia, Jean; Coustet, Baptiste; Cottin, Vincent; Boissier, Marie-Christophe; Wallaert, Benoit; Schaeverbeke, Thierry; Dastot le Moal, Florence; Frazier, Aline; Ménard, Christelle; Soubrier, Martin; Saidenberg, Nathalie; Valeyre, Dominique; Amselem, Serge; Boileau, Catherine; Crestani, Bruno; Dieudé, Philippe

2017-05-01

Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases might share additional risk factors, including FPF-linked genes. Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a discrete number of FPF-linked genes and performed a burden test to assess the excess number of mutations in RA-ILD patients compared to controls.Among the 101 RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the TERT , RTEL1 , PARN or SFTPC coding regions . The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of TERT , RTEL1 , PARN or SFTPC mutations in RA-ILD patients (OR 3.17, 95% CI 1.53-6.12; p=9.45×10 -4 ). Telomeres were shorter in RA-ILD patients with a TERT , RTEL1 or PARN mutation than in controls (p=2.87×10 -2 ).Our results support the contribution of FPF-linked genes to RA-ILD susceptibility. Copyright ©ERS 2017.

Krása a nesmrteľnosť. O plodení u Platóna a Shakespeara (Beauty and Immortality. On Procreation in Plato and Shakespeare

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Anton Vydra

2007-03-01

Full Text Available There are two moments referred in this essay: (1 A human being, which desires for immortality, desires for to be alive in his child or in an artwork. (2 Full human being’s desire is related for beauty. Is a beauty the same thing as immortality? How looks the relation between them? Shakespeare’s Sonnets begin with the challenge to his friend to procreate the offspring, because this is a way for immortality of the friend’s beauty. And if it is not a child, than verse refused him before the death or the Lethe. Similarly, Plato’s Socrates says in Symposium about his meeting with Diotima of Mantineia. She told him the oration on real Beauty without accidents. To see real Beauty means to be immortal, likewise the gods. Thus, could be a human being immortal?

New observations on the miniature of the vision of Saint Gregory of Nazianzus in Paris. GR. 510

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Gavrilović Zaga

2007-01-01

Full Text Available The article deals with the iconography of the illustration of the Second Paschal Homily of St. Gregory of Nazianzus on fol. 285r of the Paris manuscript. It questions the identity of the woman saint represented on the right of St. Paraskeve in the lower register of the scene. Unlike that above St. Paraskeve, the inscription identifying this second woman saint is fragmentary and difficult to read, but it has been widely accepted that she is Saint Helena, mother of the Emperor Constantine the Great. On the basis of two other representations of Helena in the same manuscript and of the style of the inscription accompanying them, as well as taking into account the importance of the theological meaning expounded by St. Gregory in his oration, it is suggested that the second woman saint may be St. Kyriake.

AVGVSTINVS HIPONENSIS, VIR CHRISTIANUS, DICENDI PERITUS: Analysis of classical influences in the proposal of Augustinian oratorical training

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Ivan Baycer Junior

2010-12-01

Full Text Available This work will expose an analysis of classical influences present in the proposal of Augustinian oratorical training, being developed in parallel with the study of concepts of rhetoric within Christianity. Aiming to note that the presentation prepared by Augustine of Hippo to the classical eloquence simultaneously reflects the rejection to his past and the ideas inherited by the Christian formation. Thus, it will realize that the old rhetorician proposes bases for a non artificial eloquence, whose bases reflect the Pauline conceptions – strongly influenced by Platonism – and the Latin rhetorical heritage, represented mainly by Cicero. Proposal developed during the fourth book of the treatise De doctrina Christiana, the focus of this study, where we see Augustine to reflect and to base the ideal of simple orator, with wise speech and non artificial. 

«Русская речь в ее крестьянском варианте». Заметки о прозе Федора Абрамова(“Russian language in its peasant form”. Notes on F. Abramov's prose

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Tamara Lönngren

1998-02-01

In this article, special attention is paid to vocabulary. There are about 200 dialect words in Abramov's novel. Some of them are used very frequently, such as robit' ‘work', kažinnyj ‘every', dak ‘so', pošto ‘why', none ‘now', žorat' ‘eat, drink', odneždy ‘once', kalit' ‘scold', etc. Many dialect words are used together with their literary counter- parts. This creates the doublets so typical of contemporary dialects, for example dom / khoromy ‘house', dvor / zaulok ‘yard', gornica / gostinaja ‘living-room'. Here the semantic group "Buildings" is singled out for closer investigation. In the life of the village nicknames play an important role. The 28 nicknames found in the novel are analyzed and commented on from the point of view of Russian folk culture.

Two-Dimensional Flow Modeling: Proceedings of the National U.S. Army Corps of Engineers-Sponsored Seminar on the Two-Dimensional Flow Modeling (1st), 7-9 July 1981,

Science.gov (United States)

1982-03-01

Niederauer (Enerly, Inc.), Lee Butler (WES), Danny Fread (NOAA). Theodor Strelkoff (Hydraulic Enuineering), Robert MacArthur (HEC), Warren Mellema (4RD), Jaime ...Mississippi, Sabine , and Neches Rivers as shown in Figures 1 and 2. Work is on-going to gradually extend this service to other Gulf Coast rivers in Texas...MEXICO FIG. 2-HURRICANE STORM SURGE FORECASTING OF SABINE AND NECHES RIVERS 16 DAM -Z - PLAN VIEW- SEC. VIEW f-f FIG. 3- DAM-BREAK FLOOD ONTO A VERY WIDE

Jackson Bar Training Structure Study

Science.gov (United States)

2015-05-01

comparison of the one-dimensional bridge hydraulic routines from: HEC - RAS , HEC -2, and WSPRO. Davis, CA: U.S. Army Corps of Engineers, Hydrologic Engineering...ER D C/ CH L TR -1 5- 4 Jackson Bar Training Structure Study Co as ta l a nd H yd ra ul ic s La bo ra to ry Jeremy A. Sharp and...Leroy Gage), a previously constructed HEC -2 model, and a previously constructed WES physical model from 1987. Three alternatives were modeled in an

Bell Canyon Test (BCT): cement development report

International Nuclear Information System (INIS)

Gulick, C.W.; Boa, J.A. Jr.; Buck, A.D.

1980-05-01

The Borehole Plugging (BHP) materials development program which has been underway at WES under Sandia sponsorship for about five years is reviewed. Development testing data for candidate grout mixtures for the BCT plug are presented. Field batching, mixing, and placement operations are discussed. Data from field samples molded during the two plug placements include strength, expansion, compressional wave velocity, dynamic modulus, density, and porosity. Microstructure and composition are compared for grout samples at ages of a few weeks and one year

Beyond the Wall: Typography from the German Democratic Republic

OpenAIRE

Carruthers, Grant; Yee, Joyce

2004-01-01

1989: The German Democratic Republic (GDR) still existed and the Berlin Wall was still standing. Communism was alive in Europe. Hard to believe now, yet only fifteen years ago, a reality. By 1990 the GDR was gone, but it lingers on in the memory of many people now as a dull, repressive, unimaginative place full of cheap plastic, grey concrete, goosestepping soldiers, sports stars with mullets, the dreaded Stasi secret police and of course, the Wall.\\ud \\ud These memories illustrate common Wes...

Geomechanical problems of an underground storage of spent nuclear fuel and their mathematic modelling

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Antonín Hájek

2007-01-01

Full Text Available The paper is devoted to the use of mathematical modelling for analysis of the thermo-mechanical (T-M processes, which are relevant for the assessment of underground repositories of the spent nuclear fuel. Wes shall discuss mathematical formulation, numerical methods and parallel alghorithms, which are capable to solve large-scale complicated and coupled 3D problems. Particularly, we show an application of the described methods and parallel computer simulations for analysis of model problems concerning the Swedish KBS3 concept of underground repository.

Knowledge Based Concepts and Artificial Intelligence: Applications to Guidance and Control.

Science.gov (United States)

1987-08-01

Ing soisple Idea : one function In gener1 toft ences Lhe oofecrAt Itt of itnotier fanc inan II tiere is a possible electrical path het- Ie ti s (It...packet. Durnlg foreard chaining, It is possible to inhibit at will qnnrtIons to tile operato or rrte gene - rally th e pracedaral accalaret ty Nikilr. lsxa...The system helo prponed ran not Wes cnsteitice tat the tins- ol wellting), andt thus the o-sor- genee can only be argoed. The overalt design proceeds In

And the Roads Lead to Nowhere : die Jungfrauenquelle und Last House on the Left als Transformationen

OpenAIRE

Köhne, Julia; Renz, Tilo

2010-01-01

Wes Cravens Last House on the Left (1972) ist ein Vorläufer des Rape-Revenge- enres, in dem auf eine Vergewaltigung gewaltsame Rache folgt. Er gehört zu denjenigen Filmen, die sich durch die Visualisierung exzessiver am Körper, am Fleisch verübter Gewalt auszeichnen und daher als Splatter bezeichnet werden. Die Entstehung des Splatterfilms wird mit der kulturellen Situation in den USA der Vietnam-Ära in Zusammenhang gebracht. Als filmische Vorläufer gelten Hitchcocks Psycho (1960) sowie frühe...

Whole-exome sequencing in amyotrophic lateral sclerosis suggests NEK1 is a risk gene in Chinese.

Science.gov (United States)

Gratten, Jacob; Zhao, Qiongyi; Benyamin, Beben; Garton, Fleur; He, Ji; Leo, Paul J; Mangelsdorf, Marie; Anderson, Lisa; Zhang, Zong-Hong; Chen, Lu; Chen, Xiang-Ding; Cremin, Katie; Deng, Hong-Weng; Edson, Janette; Han, Ying-Ying; Harris, Jessica; Henders, Anjali K; Jin, Zi-Bing; Li, Zhongshan; Lin, Yong; Liu, Xiaolu; Marshall, Mhairi; Mowry, Bryan J; Ran, Shu; Reutens, David C; Song, Sharon; Tan, Li-Jun; Tang, Lu; Wallace, Robyn H; Wheeler, Lawrie; Wu, Jinyu; Yang, Jian; Xu, Huji; Visscher, Peter M; Bartlett, Perry F; Brown, Matthew A; Wray, Naomi R; Fan, Dongsheng

2017-11-17

Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease characterised by the degeneration of motor neurons, which are responsible for voluntary movement. There remains limited understanding of disease aetiology, with median survival of ALS of three years and no effective treatment. Identifying genes that contribute to ALS susceptibility is an important step towards understanding aetiology. The vast majority of published human genetic studies, including for ALS, have used samples of European ancestry. The importance of trans-ethnic studies in human genetic studies is widely recognised, yet a dearth of studies of non-European ancestries remains. Here, we report analyses of novel whole-exome sequencing (WES) data from Chinese ALS and control individuals. WES data were generated for 610 ALS cases and 460 controls drawn from Chinese populations. We assessed evidence for an excess of rare damaging mutations at the gene level and the gene set level, considering only singleton variants filtered to have allele frequency less than 5 × 10 -5 in reference databases. To meta-analyse our results with a published study of European ancestry, we used a Cochran-Mantel-Haenszel test to compare gene-level variant counts in cases vs controls. No gene passed the genome-wide significance threshold with ALS in Chinese samples alone. Combining rare variant counts in Chinese with those from the largest WES study of European ancestry resulted in three genes surpassing genome-wide significance: TBK1 (p = 8.3 × 10 -12 ), SOD1 (p = 8.9 × 10 -9 ) and NEK1 (p = 1.1 × 10 -9 ). In the Chinese data alone, SOD1 and NEK1 were nominally significantly associated with ALS (p = 0.04 and p = 7 × 10 -3 , respectively) and the case/control frequencies of rare coding variants in these genes were similar in Chinese and Europeans (SOD1: 1.5%/0.2% vs 0.9%/0.1%, NEK1 1.8%/0.4% vs 1.9%/0.8%). This was also true for TBK1 (1.2%/0.2% vs 1.4%/0.4%), but

السياق واللفظ عند التراثيين علماء الأصول أنموذجا Context and pronunciation when Turathein assets scientists model

Directory of Open Access Journals (Sweden)

Professor: NAZIRA Bin Zayed Assistant Professor أستاذة مساعدة نضيرة بن زايد

2017-06-01

Full Text Available Context as phenomenion was instrested by numerous arabic scieutists with their different ideologies, because it contributed to explain and expose the real sense of any ortion, where it is linguistic, literary critical or religious ... etc.for the occidental scientists the context is combined with what we call pragmatism. the real sense What is important for us in this research is to focuse on context and the word and their importance for for arabs generally and for fundamentalists specially.in deed, the quranic speech contains a conuictional concepts and a religious verdicts which must be explained conectly to avoid the wrong interpretation.therefor, the fundamentalists emphasized greatly on the occasion and the reason of each quranic verse . Consequently, there is an interference relationship between the context and the word, they are two sides to are coin, which isto realize the right sense, that the orator wanted to send.

X-linked Hyper IgM Syndrome Presenting as Pulmonary Alveolar Proteinosis.

Science.gov (United States)

Gallagher, Joel; Adams, Juan; Hintermeyer, Mary; Torgerson, Troy R; Lopez-Guisa, Jesus; Ochs, Hans D; Szabo, Sara; Salib, Mina; Verbsky, James; Routes, John

2016-08-01

X-linked hyper IgM syndrome (XHIGM) is a combined immunodeficiency caused by mutations in the CD40 ligand (CD40L) gene that typically results in decreased or absent CD40L expression on activated T cells, leading to defective class switching and somatic hypermutation. We describe an infant who presented with respiratory failure due to pulmonary alveolar proteinosis (PAP) with a novel damaging missense mutation in the CD40L gene. Whole exome sequencing (WES) was used to identify a mutation in the CD40L gene. CD40L expression and function were determined by flow cytometry. A 5-month-old previously-healthy male presented with respiratory failure and diffuse pulmonary ground glass opacities on CT scan of the chest. Laboratory evaluation revealed an undetectable IgG, normal IgA, and elevated IgM. A bronchoalveolar lavage demonstrated pulmonary alveolar proteinosis. WES demonstrated a c.608G > C mutation in the CD40L gene resulting in p.R203T. Flow cytometry demonstrated normal CD40L expression on activated T cells but absent binding of CD40-Ig to CD40L on activated patient T cells. The clinical manifestations of XHIGM in our patient had several unique features, including the presentation with PAP, normal serum IgA, and expression of non-functional CD40L on activated T cells. To our knowledge, this is the first published case of PAP in a patient with XHIGM.

Whole-exome sequencing reveals the spectrum of gene mutations and the clonal evolution patterns in paediatric acute myeloid leukaemia.

Science.gov (United States)

Shiba, Norio; Yoshida, Kenichi; Shiraishi, Yuichi; Okuno, Yusuke; Yamato, Genki; Hara, Yusuke; Nagata, Yasunobu; Chiba, Kenichi; Tanaka, Hiroko; Terui, Kiminori; Kato, Motohiro; Park, Myoung-Ja; Ohki, Kentaro; Shimada, Akira; Takita, Junko; Tomizawa, Daisuke; Kudo, Kazuko; Arakawa, Hirokazu; Adachi, Souichi; Taga, Takashi; Tawa, Akio; Ito, Etsuro; Horibe, Keizo; Sanada, Masashi; Miyano, Satoru; Ogawa, Seishi; Hayashi, Yasuhide

2016-11-01

Acute myeloid leukaemia (AML) is a molecularly and clinically heterogeneous disease. Targeted sequencing efforts have identified several mutations with diagnostic and prognostic values in KIT, NPM1, CEBPA and FLT3 in both adult and paediatric AML. In addition, massively parallel sequencing enabled the discovery of recurrent mutations (i.e. IDH1/2 and DNMT3A) in adult AML. In this study, whole-exome sequencing (WES) of 22 paediatric AML patients revealed mutations in components of the cohesin complex (RAD21 and SMC3), BCORL1 and ASXL2 in addition to previously known gene mutations. We also revealed intratumoural heterogeneities in many patients, implicating multiple clonal evolution events in the development of AML. Furthermore, targeted deep sequencing in 182 paediatric AML patients identified three major categories of recurrently mutated genes: cohesion complex genes [STAG2, RAD21 and SMC3 in 17 patients (8·3%)], epigenetic regulators [ASXL1/ASXL2 in 17 patients (8·3%), BCOR/BCORL1 in 7 patients (3·4%)] and signalling molecules. We also performed WES in four patients with relapsed AML. Relapsed AML evolved from one of the subclones at the initial phase and was accompanied by many additional mutations, including common driver mutations that were absent or existed only with lower allele frequency in the diagnostic samples, indicating a multistep process causing leukaemia recurrence. © 2016 John Wiley & Sons Ltd.

Common Variable Immunodeficiency Caused by FANC Mutations.

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Sekinaka, Yujin; Mitsuiki, Noriko; Imai, Kohsuke; Yabe, Miharu; Yabe, Hiromasa; Mitsui-Sekinaka, Kanako; Honma, Kenichi; Takagi, Masatoshi; Arai, Ayako; Yoshida, Kenichi; Okuno, Yusuke; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Muramatsu, Hideki; Kojima, Seiji; Hira, Asuka; Takata, Minoru; Ohara, Osamu; Ogawa, Seishi; Morio, Tomohiro; Nonoyama, Shigeaki

2017-07-01

Common variable immunodeficiency (CVID) is the most common adult-onset primary antibody deficiency disease due to various causative genes. Several genes, which are known to be the cause of different diseases, have recently been reported as the cause of CVID in patients by performing whole exome sequencing (WES) analysis. Here, we found FANC gene mutations as a cause of adult-onset CVID in two patients. B cells were absent and CD4 + T cells were skewed toward CD45RO + memory T cells. T-cell receptor excision circles (TRECs) and signal joint kappa-deleting recombination excision circles (sjKRECs) were undetectable in both patients. Both patients had no anemia, neutropenia, or thrombocytopenia. Using WES, we identified compound heterozygous mutations of FANCE in one patient and homozygous mutation of FANCA in another patient. The impaired function of FANC protein complex was confirmed by a monoubiquitination assay and by chromosome fragility test. We then performed several immunological evaluations including quantitative lymphocyte analysis and TRECs/sjKRECs analysis for 32 individuals with Fanconi anemia (FA). In total, 22 FA patients (68.8%) were found to have immunological abnormalities, suggesting that such immunological findings may be common in FA patients. These data indicate that FANC mutations are involved in impaired lymphogenesis probably by the accumulation of DNA replication stress, leading to CVID. It is important to diagnose FA because it drastically changes clinical management. We propose that FANC mutations can cause isolated immunodeficiency in addition to bone marrow failure and malignancy.

Mutations in plasmalemma vesicle-associated protein cause severe syndromic protein-losing enteropathy.

Science.gov (United States)

Broekaert, Ilse Julia; Becker, Kerstin; Gottschalk, Ingo; Körber, Friederike; Dötsch, Jörg; Thiele, Holger; Altmüller, Janine; Nürnberg, Peter; Hünseler, Christoph; Cirak, Sebahattin

2018-04-16

Protein-losing enteropathy (PLE) is characterised by gastrointestinal protein leakage due to loss of mucosal integrity or lymphatic abnormalities. PLE can manifest as congenital diarrhoea and should be differentiated from other congenital diarrhoeal disorders. Primary PLEs are genetically heterogeneous and the underlying genetic defects are currently emerging. We report an infant with fatal PLE for whom we aimed to uncover the underlying pathogenic mutation. We performed whole exome sequencing (WES) for the index patient. Variants were classified based on the American College of Medical Genetics and Genomics guidelines. WES results and our detailed clinical description of the patient were compared with the literature. We discovered a novel homozygous stop mutation (c.988C>T, p.Q330*) in the Plasmalemma Vesicle-Associated Protein ( PLVAP ) gene in a newborn with fatal PLE, facial dysmorphism, and renal, ocular and cardiac anomalies. The Q330* mutation is predicted to result in complete loss of PLVAP protein expression leading to deletion of the diaphragms of endothelial fenestrae, resulting in plasma protein extravasation and PLE. Recently, another single homozygous stop mutation in PLVAP causing lethal PLE in an infant was reported. Our findings validate PLVAP mutations as a cause of syndromic PLE. Prenatal anomalies, severe PLE and syndromic features may guide the diagnosis of this rare disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Evaluation of performance of CMIP5 models in simulating the North Pacific Oscillation and El Niño Modoki

Science.gov (United States)

Wang, Xin; Chen, Mengyan; Wang, Chunzai; Yeh, Sang-Wook; Tan, Wei

2018-04-01

Previous observational studies have documented that the occurrence frequency of El Niño Modoki is closely linked to the North Pacific Oscillation (NPO). The present paper evaluates the relationships between the frequency of El Niño Modoki and the NPO in the historical runs of the Coupled Model Intercomparison Project Phase 5 (CMIP5) and examines the related physical processes. It is found that six of 25 CMIP5 models can reproduce both the spatial patterns of the NPO and El Niño Modoki. Four of these six models exhibit good performance in simulating the positive correlation between the NPO index and the frequency of El Niño Modoki. The analyses further show that the key physical processes determining the relationships between the NPO and the frequency of El Niño Modoki are the intensity of wind-evaporation-SST (WES) feedback in the subtropical northeastern North Pacific. This study enhances the understanding of the connections between the North Pacific mid-latitude climate system and El Niño Modoki, and has an important implication for the change of El Niño Modoki under global warming. If global warming favors to produce an oceanic and atmospheric pattern similar to the positive phase of the NPO in the North Pacific, more El Niño Modoki events will occur in the tropical Pacific with the assistance of the WES feedback processes.

HABP2 p.G534E variant in patients with family history of thyroid and breast cancer

Science.gov (United States)

Pinheiro, Maisa; Drigo, Sandra Aparecida; Tonhosolo, Renata; Andrade, Sonia C.S.; Marchi, Fabio Albuquerque; Jurisica, Igor; Kowalski, Luiz Paulo; Achatz, Maria Isabel; Rogatto, Silvia Regina

2017-01-01

Familial Papillary Thyroid Carcinoma (PTC) has been described as a hereditary predisposition cancer syndrome associated with mutations in candidate genes including HABP2. Two of 20 probands from families with history of PTC and breast carcinoma (BC) were evaluated by whole exome sequencing (WES) revealing HABP2 p.G534E. Sanger sequencing was used to confirm the involvement of this variant in three families (F1: 7 relatives; F2: 3 and F3: 3). The proband and his sister (with no malignant tumor so far) from F1 were homozygous for the variant whereas one relative with PTC from F2 was negative for the variant. Although the proband of the F3 with PTC was HABP2 wild type, three relatives presented the variant. Five of 170 healthy Brazilian individuals with no family history of BC or PTC and three of 50 sporadic PTC presented the p.G534E. These findings suggested no association of this variant with our familial PTC cases. Genes potentially associated with deregulation of the extracellular matrix organization pathway (CTSB, TNXB, COL4A3, COL16A1, COL24A1, COL5A2, NID1, LOXL2, MMP11, TRIM24 and MUSK) and DNA repair function (NBN and MSH2) were detected by WES, suggesting that other cancer-associated genes have pathogenic effects in the risk of familial PTC development. PMID:28402931

Mutations in fetal genes involved in innate immunity and host defense against microbes increase risk of preterm premature rupture of membranes (PPROM).

Science.gov (United States)

Modi, Bhavi P; Teves, Maria E; Pearson, Laurel N; Parikh, Hardik I; Haymond-Thornburg, Hannah; Tucker, John L; Chaemsaithong, Piya; Gomez-Lopez, Nardhy; York, Timothy P; Romero, Roberto; Strauss, Jerome F

2017-11-01

Twin studies have revealed a significant contribution of the fetal genome to risk of preterm birth. Preterm premature rupture of membranes (PPROM) is the leading identifiable cause of preterm delivery. Infection and inflammation of the fetal membranes is commonly found associated with PPROM. We carried out whole exome sequencing (WES) of genomic DNA from neonates born of African-American mothers whose pregnancies were complicated by PPROM (76) or were normal term pregnancies (N = 43) to identify mutations in 35 candidate genes involved in innate immunity and host defenses against microbes. Targeted genotyping of mutations in the candidates discovered by WES was conducted on an additional 188 PPROM cases and 175 controls. We identified rare heterozygous nonsense and frameshift mutations in several of the candidate genes, including CARD6, CARD8, DEFB1, FUT2, MBL2, NLP10, NLRP12, and NOD2. We discovered that some mutations (CARD6, DEFB1, FUT2, MBL2, NLRP10, NOD2) were present only in PPROM cases. We conclude that rare damaging mutations in innate immunity and host defense genes, the majority being heterozygous, are more frequent in neonates born of pregnancies complicated by PPROM. These findings suggest that the risk of preterm birth in African-Americans may be conferred by mutations in multiple genes encoding proteins involved in dampening the innate immune response or protecting the host against microbial infection and microbial products. © 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Comprehensive investigation of CASK mutations and other genetic etiologies in 41 patients with intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH.

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Shin Hayashi

Full Text Available The CASK gene (Xp11.4 is highly expressed in the mammalian nervous system and plays several roles in neural development and synaptic function. Loss-of-function mutations of CASK are associated with intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH, especially in females. Here, we present a comprehensive investigation of 41 MICPCH patients, analyzed by mutational search of CASK and screening of candidate genes using an SNP array, targeted resequencing and whole-exome sequencing (WES. In total, we identified causative or candidate genomic aberrations in 37 of the 41 cases (90.2%. CASK aberrations including a rare mosaic mutation in a male patient, were found in 32 cases, and a mutation in ITPR1, another known gene in which mutations are causative for MICPCH, was found in one case. We also found aberrations involving genes other than CASK, such as HDAC2, MARCKS, and possibly HS3ST5, which may be associated with MICPCH. Moreover, the targeted resequencing screening detected heterozygous variants in RELN in two cases, of uncertain pathogenicity, and WES analysis suggested that concurrent mutations of both DYNC1H1 and DCTN1 in one case could lead to MICPCH. Our results not only identified the etiology of MICPCH in nearly all the investigated patients but also suggest that MICPCH is a genetically heterogeneous condition, in which CASK inactivating mutations appear to account for the majority of cases.

Information Support of Optimal Control of Modes of Electric Systems with Renewable Energy Sources

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Michalina Gryniewicz-Jaworska

2017-12-01

Full Text Available To provide necessary quality of electric energy and reliable supply and reduce environmental contamination as a result of energy units operation, renewable sources of energy (RSE, in particular solar electric stations (SES, wind electric stations (WES and small hydropower stations (SHES are intensively developed. The paper considers the conditions of optimality of renewable sources of energy (RSE functioning in electric systems, controllability of which is limited by the impact of non-stable weather conditions. The influence of control system information support on the efficiency of RSE usage is shown.

Reassessment of liquefaction potential and estimation of earthquake- induced settlements at Paducah Gaseous Diffusion Plant, Paducah, Kentucky. Final report

International Nuclear Information System (INIS)

Sykora, D.W.; Yule, D.E.

1996-04-01

This report documents a reassessment of liquefaction potential and estimation of earthquake-induced settlements for the U.S. Department of Energy (DOE), Paducah Gaseous Diffusion Plant (PGDP), located southwest of Paducah, KY. The U.S. Army Engineer Waterways Experiment Station (WES) was authorized to conduct this study from FY91 to FY94 by the DOE, Oak Ridge Operations (ORO), Oak Ridge, TN, through Inter- Agency Agreement (IAG) No. DE-AI05-91OR21971. The study was conducted under the Gaseous Diffusion Plant Safety Analysis Report (GDP SAR) Program

Disease evolution and outcomes in familial AML with germline CEBPA mutations

DEFF Research Database (Denmark)

Tawana, Kiran; Wang, Jun; Renneville, Aline

2015-01-01

collected from 10 CEBPA-mutated families, representing 24 members with acute myeloid leukemia (AML). Whole-exome (WES) and deep sequencing were performed to genetically profile tumors and define patterns of clonal evolution. Germline CEBPA mutations clustered within the N-terminal and were highly penetrant......, with AML presenting at a median age of 24.5 years (range, 1.75-46 years). In all diagnostic tumors tested (n = 18), double CEBPA mutations (CEBPAdm) were detected, with acquired (somatic) mutations preferentially targeting the C-terminal. Somatic CEBPA mutations were unstable throughout the disease course...

Fiberglass Material Specification Test Support

Science.gov (United States)

1985-09-27

samples show a significant penetration at 600 C followed by expansion of the glass-filled matrix. One expected cause for such behavior would be that...but instead showed only an expansion after 60 0 C. This behavior could be interpreted as the presence of glass fiber at or near the surface of the...wan opp4od by Wash (70/m 42 setome wes cosumed in Phue I -sIf duplicate ^- 0,5am 0"• layer). T1 Olcost Was allowed to cu to 8 espoimus. 2 not oyam, aid

’n Ondersoek na die bronne van werkstevredenheid en werkstres onder middelvlakbestuurders in die Wes-Kaap

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S. C. Strydom

2002-09-01

Full Text Available The general aim of the study is to investigate the different attitudes and perceptions of middle level managers with regard to sources of job satisfaction, sources which contribute to job dissatisfaction, and to job stress. In this regard it was decided to make use of triangulation by which qualitative and quantitative research methods are used. Thematic analysis is used on the qualitative level to identify the possible sources of job satisfaction, dissatisfaction and job stress. This method is quantitatively supported by a determination of the frequencies and percentages of subject responses by means of semi structured interviews. On the qualitative level it was found that the experience of success is rated as the most important source of job satisfaction and that interpersonal relationships are the most significant source of job dissatisfaction. Finally it seems that work expectations/ demands appear to be the major source of job stress. Opsomming Die algemene doelstelling van die studie is om ondersoek in te stel na die verskillende houdings en persepsies van middelvlak-bestuurders rakende werkstevredenheid, sowel as die bronne wat bydra tot werkstres en werksontevredenheid. In dié verband is besluit om van triangulasie gebruik te maak. Op die kwalitatiewe vlak word tematiese analise gebruik om potensiële bronne van werkstevredenheid, ontevredenheid en werkstres te identifiseer. Hierdie metode word verder kwantitatief ondersteun deur ‘n bepaling van frekwensies en persentasies van subjekte se reponse wat uit semi-gestruktureerde onderhoude verkry is. Op die kwalitatiewe vlak blyk dit dat die ervaring van sukses die grootste bron van werkstevredenheid is en dat interpersoonlike verhoudings die bron is wat die meeste bydra tot ontevredenheid. Verder blyk dit dat werksverwagtinge/-eise die grootste bron van werkstres is.

Studies on productivity lodge resistance of radiation induced mutants of syrian local durum wheat

Energy Technology Data Exchange (ETDEWEB)

Elfares, A M; Ghazal, H M [Dep. of Radiation Agriculture, Syrian Atomic Energy Commision, Damascus, P.O. Box 6091, (Syrian Arab Republic)

1995-10-01

The aim of the research was to induce mutations characterized by lodging resistant and high yielding ability in two syrian local durum wheat land races. This research was carried out at two periods during 1983-1987 and from 1991-1993. At the first period, Kernels of Hourani and Senatore Cappelle were treated with 10, 15, 20, 25 and 30 K rad of gamma rays at the Laboratory of the commission of Syrian Atomic Energy to induce mutations. The treated Kernels were planted in 1983/1984 season. After that, selection were practicised on plants which characterized by good performance and lodging resistant. During the successive seasons, screening were made on mutant lines to keep out only lines which show adaptability to intensive cultivation. Second period includes testing of selected lines at two govern orates of syria (Raqqa and Aleppo) during three successive seasons; 1991/1992 and 1992/1993 under intensive cultivation conditions (fertilization, irrigation, stands, etc.).

JEREMIAD FRAMES IN REAGAN’S INAUGURAL ADDRESSES

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Mister Gidion Maru

2013-04-01

Full Text Available This research attempts to examine the existence of frames from jeremiad tradition as part of American values in an American president’s inaugural address. The function and context of the frames are also investigated. These aims are achieved by applying Goffman’s Frame Analysis on the text of Reagan’s inaugural addresses. This inaugural addresses is chosen because Reagan’s presidency is regarded to set the tone for the following presidencies; his presidency faced crises which other presidents following him have also faced; and he is viewed as one of the best orators among American presidents. The results show that Ronald Reagan’s inaugural addresses use the jeremiad frames which are categorized into three forms, namely, the lamentation of the present, the evocation of the past and the calling for renewal. By using these frames in combination with the context of the inaugural address, Reagan presents American perspective and hopes for their situation and future.

AN ORTHODOX THINKER AND A ROMANIAN HEART: THE SAINT HIERARCH ANTHIM

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Henrieta Anişoara ŞERBAN

2016-10-01

Full Text Available 2016 is an anniversary year, dedicated to the Saint Hierarch Anthim, a multi-faced personality of Georgian origin, but with a Romanian accomplished life. He was a true Orthodox believer, a Hierarch of our Orthodox Church in Wallachia and a deep thinker, who lived through the teachings of the faith. At the same time, he was a good manager and a philanthropist, a scholar, a polyglot, a calligrapher, a typographer, a Church architect, an orator turned writer, a painter and a sculptor. His great homiletic work entitled Didahiile sends to Didache, the oldest post-Bible Christian text, famous at Constantinople, known also as The Teachings of the Twelve Apostles (The Teachings of the Lord to the Gentiles (or Nations by the Twelve Apostles. The study approaches and develops these dimensions of the personality and of the thought of the Saint Hierarch Anthim, in order to emphasize both his life and his work as an esteemed symbol of the Orthodox faith.

Tradition as the genealogy of truth Hippocrates and Boerhaave between assimilation, variation and deviation.

Science.gov (United States)

Lo Presti, Roberto

2010-01-01

It is a matter of fact that rarely in the history of modern medicine has a physician gained such immediate and universal fame, and rarely has his contribution to medical knowledge and teaching been so promptly and almost unanimously recognized as a fundamental and, so to speak, a foundational one, as in the case of Boerhaave. In fact, the contribution he gave to provide medicine with a 'scientific' framework, and medical teaching with solid methodological bases, proved decisive. Otherwise, his appraisal of the Ancients (and especially of Hippocrates) and his will to refer to Hippocrates as a model for medical teaching were proverbial. Taking the corpus of his orations as a point of reference, I will thus try to elucidate 1) Boerhaave's main focus and theoretical goals; 2) the argumentative and methodological strategies he adopted in order to achieve them; 3) the position that the key-concept of 'tradition', the figure of Hippocrates, and the notion of 'Hippocratism' hold within these strategies.

Claudia Quinta (Pro Caelio 34 and an altar to Magna Mater

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Eleanor Winsor Leach

2010-11-01

Full Text Available Among the items of sculpture from the Capitoline collection now housed in the Museum of the Power Station Montemartini is a marble relief altar of the Claudian Period (E. Simon's dating dedicated to the mater deorum and the navis salvia and depicting the arrival of the goddess Cybele at Rome by ship. The dedicator is one Claudia Syntyche and the sculpture alludes to the legends attached to a much honored woman of the Claudian family whom Cicero, in his oration pro Caelio brought on stage in a cameo appearance to bolster his case against the controversial contemporary woman Clodia Metelli as one of the accusers of his client M. Caelius Rufus. This paper will consider questions raised by the iconography of the altar with reference to the development of Claudia's legend in Roman mythology and subsequently ask who was this Claudia the dedicator and why did she choose Magna Mater for her vow?

Scattering Correction For Image Reconstruction In Flash Radiography

Energy Technology Data Exchange (ETDEWEB)

Cao, Liangzhi; Wang, Mengqi; Wu, Hongchun; Liu, Zhouyu; Cheng, Yuxiong; Zhang, Hongbo [Xi' an Jiaotong Univ., Xi' an (China)

2013-08-15

Scattered photons cause blurring and distortions in flash radiography, reducing the accuracy of image reconstruction significantly. The effect of the scattered photons is taken into account and an iterative deduction of the scattered photons is proposed to amend the scattering effect for image restoration. In order to deduct the scattering contribution, the flux of scattered photons is estimated as the sum of two components. The single scattered component is calculated accurately together with the uncollided flux along the characteristic ray, while the multiple scattered component is evaluated using correction coefficients pre-obtained from Monte Carlo simulations.The arbitrary geometry pretreatment and ray tracing are carried out based on the customization of AutoCAD. With the above model, an Iterative Procedure for image restORation code, IPOR, is developed. Numerical results demonstrate that the IPOR code is much more accurate than the direct reconstruction solution without scattering correction and it has a very high computational efficiency.

Scattering Correction For Image Reconstruction In Flash Radiography

International Nuclear Information System (INIS)

Cao, Liangzhi; Wang, Mengqi; Wu, Hongchun; Liu, Zhouyu; Cheng, Yuxiong; Zhang, Hongbo

2013-01-01

Scattered photons cause blurring and distortions in flash radiography, reducing the accuracy of image reconstruction significantly. The effect of the scattered photons is taken into account and an iterative deduction of the scattered photons is proposed to amend the scattering effect for image restoration. In order to deduct the scattering contribution, the flux of scattered photons is estimated as the sum of two components. The single scattered component is calculated accurately together with the uncollided flux along the characteristic ray, while the multiple scattered component is evaluated using correction coefficients pre-obtained from Monte Carlo simulations.The arbitrary geometry pretreatment and ray tracing are carried out based on the customization of AutoCAD. With the above model, an Iterative Procedure for image restORation code, IPOR, is developed. Numerical results demonstrate that the IPOR code is much more accurate than the direct reconstruction solution without scattering correction and it has a very high computational efficiency

Theorizing plurivocal dialogue

DEFF Research Database (Denmark)

Bager, Ann

2014-01-01

The present chapter explores a Bakhtinian perspective on dialogicality and its implications for participatory research processes in the field of organi- zational and leadership studies. In addition to Bakhtin, the theoretical basis stems from notions from Foucauldian governmentality and organizat......The present chapter explores a Bakhtinian perspective on dialogicality and its implications for participatory research processes in the field of organi- zational and leadership studies. In addition to Bakhtin, the theoretical basis stems from notions from Foucauldian governmentality...... and organizational discourse studies. These perspectives are elaborated on and implemented to frame, discuss and criticize the methodological basis of a case study which the author helped to initiate: a plurivocal, participatory research- based leadership forum involving professional leaders, researchers...... as the theoretical basis for the analysis. The article discusses how the Bakhtinian conception of dialogue offers a particular way of framing power, participation, meaning-making, knowledge pro- duction, and identity work in relation to the leadership forum and collab- orative research processes in general...

Bringing Federated Identity to Grid Computing

Energy Technology Data Exchange (ETDEWEB)

Teheran, Jeny [Fermilab

2016-03-04

The Fermi National Accelerator Laboratory (FNAL) is facing the challenge of providing scientific data access and grid submission to scientific collaborations that span the globe but are hosted at FNAL. Users in these collaborations are currently required to register as an FNAL user and obtain FNAL credentials to access grid resources to perform their scientific computations. These requirements burden researchers with managing additional authentication credentials, and put additional load on FNAL for managing user identities. Our design integrates the existing InCommon federated identity infrastructure, CILogon Basic CA, and MyProxy with the FNAL grid submission system to provide secure access for users from diverse experiments and collab orations without requiring each user to have authentication credentials from FNAL. The design automates the handling of certificates so users do not need to manage them manually. Although the initial implementation is for FNAL's grid submission system, the design and the core of the implementation are general and could be applied to other distributed computing systems.

Para uma história das instituições universitárias: uma contribuição portuguesa fundamental

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Francisco Gama Caeiro

1977-09-01

Full Text Available (primeiro parágrafo do artigo Não se pode atribuir a mera negligência, mas antes a um conjunto de circunstâncias muito mais complexo, o recíproco distanciamento entre estudiosos brasileiros e portugueses, e, ainda mais, o mútuo desconhecimento das culturas que, no mesmo idioma, se produzem nas duas margens do Atlântico: a asserção, de tanto repetida, se converteu em retórico lugar comum, em oratória de discurso obrigado a mote, em glosa elegíaca de jornal. Mas, o fato incontroverso — sem agora buscar explicações para ele — é que tal afastamento tem existido, não obstante os persistentes esforços desenvolvidos para o contrariar, sendo a produção bibliográfica, que parece por vezes processar-se em compartimentos estanques, o forçoso reflexo dessa situação.

Gross o, 1957-1973

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Silvia Helena Andrade de Brito

2007-01-01

Full Text Available This article has as object the Cidade Dom Bosco (named as Escola Alexandre Aurélio de Castro in 1957, when it was opened, situated in Dom Bosco neighbourhood. We observed and analysed the parameters and guidelines of the Salesian education from 1957 to 1973. It discusses how this educational institute was implanted. The objective of the institute was to integrate the working class students into society. The nucleous of this action was the Salesian ethos for education, based on Dom Bosco’s ‘preventive system’, aiming at materializing the so named Escola Oratório. This way, it had particular characteristics in relation to the other Salesian initiatives, as it created to support the working class of the city where it is located. Also, through this institution, the Salesian social project was extended and it considers the school as the way for not to leave the working class condition, but as a mean to rise socially in the same universe.

The difficulties of Biocommunication

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Borrelli Eugenio

2002-09-01

Full Text Available Communicating modern biotechnologies is certainly no easy task. To tackle such a complex and future-oriented assignment, help may arrive, paradoxically, from the past, from ancient rhetorical tradition, and in particular from Aristotle, the most renowned rhetoric teacher of all time. In his Rhetoric, Aristotle suggested that to be persuasive speakers should make use of widely accepted opinions (endoxa, i.e. the common sense shared by all. Common sense is expressed in common truths and value-laden maxims. Common sense, however, is not flat but dialectical, in that it includes contrasting subjects. While reasoning, orators do not just passively report a conception of an unchanging world, but they reproduce the contrasting conceptions included in common sense. In the case of the debate about Biotechnologies, the contrasting conceptions can be found in the Natural/Artificial dualism, in the dichotomy between an attitude marked by obscurantism and suspicion of scientific and technological innovation and that of a scientistic attitude

Newborn Screening in the Era of Precision Medicine.

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Yang, Lan; Chen, Jiajia; Shen, Bairong

2017-01-01

As newborn screening success stories gained general confirmation during the past 50 years, scientists quickly discovered diagnostic tests for a host of genetic disorders that could be treated at birth. Outstanding progress in sequencing technologies over the last two decades has made it possible to comprehensively profile newborn screening (NBS) and identify clinically relevant genomic alterations. With the rapid developments in whole-genome sequencing (WGS) and whole-exome sequencing (WES) recently, we can detect newborns at the genomic level and be able to direct the appropriate diagnosis to the different individuals at the appropriate time, which is also encompassed in the concept of precision medicine. Besides, we can develop novel interventions directed at the molecular characteristics of genetic diseases in newborns. The implementation of genomics in NBS programs would provide an effective premise for the identification of the majority of genetic aberrations and primarily help in accurate guidance in treatment and better prediction. However, there are some debate correlated with the widespread application of genome sequencing in NBS due to some major concerns such as clinical analysis, result interpretation, storage of sequencing data, and communication of clinically relevant mutations to pediatricians and parents, along with the ethical, legal, and social implications (so-called ELSI). This review is focused on these critical issues and concerns about the expanding role of genomics in NBS for precision medicine. If WGS or WES is to be incorporated into NBS practice, considerations about these challenges should be carefully regarded and tackled properly to adapt the requirement of genome sequencing in the era of precision medicine.

Autistic Siblings with Novel Mutations in Two Different Genes: Insight for Genetic Workups of Autistic Siblings and Connection to Mitochondrial Dysfunction

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Barrett J. Burger

2017-10-01

Full Text Available The prevalence of autism spectrum disorder (ASD is high, yet the etiology of this disorder is still uncertain. Advancements in genetic analysis have provided the ability to identify potential genetic changes that may contribute to ASD. Interestingly, several genetic syndromes have been linked to metabolic dysfunction, suggesting an avenue for treatment. In this case study, we report siblings with ASD who had similar initial phenotypic presentations. Whole exome sequencing (WES revealed a novel c.795delT mutation in the WDR45 gene affecting the girl, which was consistent with her eventual progression to a Rett-like syndrome phenotype including seizures along with a stereotypical cyclic breathing pattern. Interestingly, WES identified that the brother harbored a novel heterozygous Y1546H variant in the DEP domain-containing protein 5 (DEPDC5 gene, consistent with his presentation. Both siblings underwent a metabolic workup that demonstrated different patterns of mitochondrial dysfunction. The girl demonstrated statistically significant elevations in mitochondrial activity of complex I + III in both muscle and fibroblasts and increased respiration in peripheral blood mononuclear cells (PBMCs on Seahorse Extracellular Flux analysis. The boy demonstrates a statistically significant decrease in complex IV activity in buccal epithelium and decreased respiration in PBMCs. These cases highlight the differences in genetic abnormalities even in siblings with ASD phenotypes as well as highlights the individual role of novel mutations in the WDR45 and DEPDC5 genes. These cases demonstrate the importance of advanced genetic testing combined with metabolic evaluations in the workup of children with ASD.

Modelling and forecasting monthly swordfish catches in the Eastern Mediterranean

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Konstantinos I. Stergiou

2003-04-01

Full Text Available In this study, we used the X-11 census technique for modelling and forecasting the monthly swordfish (Xiphias gladius catches in the Greek Seas during 1982-1996 and 1997 respectively, using catches reported by the National Statistical Service of Greece (NSSG. Forecasts built with X-11 were also compared with those derived from ARIMA andWinter’s exponential smoothing (WES models. The X-11 method captured the features of the study series and outperformed the other two methods, in terms of both fitting and forecasting performance, for all the accuracy measures used. Thus, with the exception of October, November and December 1997, when the corresponding absolute percentage error(APE values were very high (as high as 178.6% because of the low level of the catches, monthly catches during the remaining months of 1997 were predicted accurately, with a mean APE of 12.5%. In contrast, the mean APE values of the other two methods for the same months were higher (ARIMA: 14.6%; WES: 16.6%. The overall good performance of X-11 andthe fact that it provides an insight into the various components (i.e. the seasonal, trend-cycle and irregular components of the time series of interest justify its use in fisheries research. The basic features of the swordfish catches revealed by the application of the X-11 method, the effect of the length of the forecasting horizon on forecasting accuracy and the accuracy of the catches reported by NSSG are also discussed.

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

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Szafranski, Przemyslaw; Gambin, Tomasz; Dharmadhikari, Avinash V; Akdemir, Kadir Caner; Jhangiani, Shalini N; Schuette, Jennifer; Godiwala, Nihal; Yatsenko, Svetlana A; Sebastian, Jessica; Madan-Khetarpal, Suneeta; Surti, Urvashi; Abellar, Rosanna G; Bateman, David A; Wilson, Ashley L; Markham, Melinda H; Slamon, Jill; Santos-Simarro, Fernando; Palomares, María; Nevado, Julián; Lapunzina, Pablo; Chung, Brian Hon-Yin; Wong, Wai-Lap; Chu, Yoyo Wing Yiu; Mok, Gary Tsz Kin; Kerem, Eitan; Reiter, Joel; Ambalavanan, Namasivayam; Anderson, Scott A; Kelly, David R; Shieh, Joseph; Rosenthal, Taryn C; Scheible, Kristin; Steiner, Laurie; Iqbal, M Anwar; McKinnon, Margaret L; Hamilton, Sara Jane; Schlade-Bartusiak, Kamilla; English, Dawn; Hendson, Glenda; Roeder, Elizabeth R; DeNapoli, Thomas S; Littlejohn, Rebecca Okashah; Wolff, Daynna J; Wagner, Carol L; Yeung, Alison; Francis, David; Fiorino, Elizabeth K; Edelman, Morris; Fox, Joyce; Hayes, Denise A; Janssens, Sandra; De Baere, Elfride; Menten, Björn; Loccufier, Anne; Vanwalleghem, Lieve; Moerman, Philippe; Sznajer, Yves; Lay, Amy S; Kussmann, Jennifer L; Chawla, Jasneek; Payton, Diane J; Phillips, Gael E; Brosens, Erwin; Tibboel, Dick; de Klein, Annelies; Maystadt, Isabelle; Fisher, Richard; Sebire, Neil; Male, Alison; Chopra, Maya; Pinner, Jason; Malcolm, Girvan; Peters, Gregory; Arbuckle, Susan; Lees, Melissa; Mead, Zoe; Quarrell, Oliver; Sayers, Richard; Owens, Martina; Shaw-Smith, Charles; Lioy, Janet; McKay, Eileen; de Leeuw, Nicole; Feenstra, Ilse; Spruijt, Liesbeth; Elmslie, Frances; Thiruchelvam, Timothy; Bacino, Carlos A; Langston, Claire; Lupski, James R; Sen, Partha; Popek, Edwina; Stankiewicz, Paweł

2016-05-01

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV.

CEP78 is mutated in a distinct type of Usher syndrome.

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Fu, Qing; Xu, Mingchu; Chen, Xue; Sheng, Xunlun; Yuan, Zhisheng; Liu, Yani; Li, Huajin; Sun, Zixi; Li, Huiping; Yang, Lizhu; Wang, Keqing; Zhang, Fangxia; Li, Yumei; Zhao, Chen; Sui, Ruifang; Chen, Rui

2017-03-01

Usher syndrome is a genetically heterogeneous disorder featured by combined visual impairment and hearing loss. Despite a dozen of genes involved in Usher syndrome having been identified, the genetic basis remains unknown in 20-30% of patients. In this study, we aimed to identify the novel disease-causing gene of a distinct subtype of Usher syndrome. Ophthalmic examinations and hearing tests were performed on patients with Usher syndrome in two consanguineous families. Target capture sequencing was initially performed to screen causative mutations in known retinal disease-causing loci. Whole exome sequencing (WES) and whole genome sequencing (WGS) were applied for identifying novel disease-causing genes. RT-PCR and Sanger sequencing were performed to evaluate the splicing-altering effect of identified CEP78 variants. Patients from the two independent families show a mild Usher syndrome phenotype featured by juvenile or adult-onset cone-rod dystrophy and sensorineural hearing loss. WES and WGS identified two homozygous rare variants that affect mRNA splicing of a ciliary gene CEP78 . RT-PCR confirmed that the two variants indeed lead to abnormal splicing, resulting in premature stop of protein translation due to frameshift. Our results provide evidence that CEP78 is a novel disease-causing gene for Usher syndrome, demonstrating an additional link between ciliopathy and Usher protein network in photoreceptor cells and inner ear hair cells. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Coherent climate anomalies over the Indo-western Pacific in post-El Niño summer

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Kosaka, Y.; Xie, S. P.; DU, Y.; Hu, K.; Chowdary, J. S.; Huang, G.

2016-12-01

El Niño typically peaks in boreal winter, and the associated equatorial Pacific sea surface temperature (SST) signal dissipates before subsequent summer. Its impact, however, outlasts until boreal summer in the Indo-western Pacific, featuring basin-wide Indian Ocean warming and tropical Northwestern Pacific cooling accompanied by the Pacific-Japan (PJ) teleconnection pattern with surface anomalous anticyclone (AAC) extending from the Philippine Sea to the northern Indian Ocean. Two formation mechanisms have been proposed for these climate anomalies in post-El Niño-Southern Oscillation (ENSO) summer. One hypothesis invokes the wind-evaporation-SST (WES) feedback in the tropical Northwestern Pacific, while the other points to inter-basin feedback between the Indian Ocean and tropical Northwestern Pacific. Based on a coupled model experiment, we propose an ocean-atmosphere coupled mode that synthesizes the two mechanisms. This Indo-western Pacific Ocean capacitor (IPOC) mode evolves seasonally from spring to summer under seasonal migration of background state. In spring, the WES feedback is operative in association with the tropical Northwestern Pacific cooling, while in summer the Indian Ocean warming and the inter-basin interaction maintains the AAC. While the IPOC mode is independent of ENSO in mechanism, ENSO can drive this mode in its decay phase. This excitation, however, has undergone substantial interdecadal modulations, depending on ENSO amplitude and persistence of Indian Ocean warming. The ENSO-IPOC correlation is high after the mid-1970s and at the beginning of the 20th century, but low in between.

Somatic APC mosaicism and oligogenic inheritance in genetically unsolved colorectal adenomatous polyposis patients.

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Ciavarella, Michele; Miccoli, Sara; Prossomariti, Anna; Pippucci, Tommaso; Bonora, Elena; Buscherini, Francesco; Palombo, Flavia; Zuntini, Roberta; Balbi, Tiziana; Ceccarelli, Claudio; Bazzoli, Franco; Ricciardiello, Luigi; Turchetti, Daniela; Piazzi, Giulia

2018-03-01

Germline variants in the APC gene cause familial adenomatous polyposis. Inherited variants in MutYH, POLE, POLD1, NTHL1, and MSH3 genes and somatic APC mosaicism have been reported as alternative causes of polyposis. However, ~30-50% of cases of polyposis remain genetically unsolved. Thus, the aim of this study was to investigate the genetic causes of unexplained adenomatous polyposis. Eight sporadic cases with >20 adenomatous polyps by 35 years of age or >50 adenomatous polyps by 55 years of age, and no causative germline variants in APC and/or MutYH, were enrolled from a cohort of 56 subjects with adenomatous colorectal polyposis. APC gene mosaicism was investigated on DNA from colonic adenomas by Sanger sequencing or Whole Exome Sequencing (WES). Mosaicism extension to other tissues (peripheral blood, saliva, hair follicles) was evaluated using Sanger sequencing and/or digital PCR. APC second hit was investigated in adenomas from mosaic patients. WES was performed on DNA from peripheral blood to identify additional polyposis candidate variants. We identified APC mosaicism in 50% of patients. In three cases mosaicism was restricted to the colon, while in one it also extended to the duodenum and saliva. One patient without APC mosaicism, carrying an APC in-frame deletion of uncertain significance, was found to harbor rare germline variants in OGG1, POLQ, and EXO1 genes. In conclusion, our restrictive selection criteria improved the detection of mosaic APC patients. In addition, we showed for the first time that an oligogenic inheritance of rare variants might have a cooperative role in sporadic colorectal polyposis onset.

Next-generation sequencing in schizophrenia and other neuropsychiatric disorders.

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Schreiber, Matthew; Dorschner, Michael; Tsuang, Debby

2013-10-01

Schizophrenia is a debilitating lifelong illness that lacks a cure and poses a worldwide public health burden. The disease is characterized by a heterogeneous clinical and genetic presentation that complicates research efforts to identify causative genetic variations. This review examines the potential of current findings in schizophrenia and in other related neuropsychiatric disorders for application in next-generation technologies, particularly whole-exome sequencing (WES) and whole-genome sequencing (WGS). These approaches may lead to the discovery of underlying genetic factors for schizophrenia and may thereby identify and target novel therapeutic targets for this devastating disorder. © 2013 Wiley Periodicals, Inc.

Dopluise (Hemiptera: Coccoidea geassosieer met die wipstertmier, Crematogaster peringueyi Emery (Hymenoptera: Formicidae

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Johannes H. Giliomee

2015-02-01

Full Text Available Neste van die wipstertmier, Crematogaster peringueyi (Hymenoptera: Formicidae, is op verskeie plekke langs die kus van die Wes-Kaap versamel. Die doel was om vas te stel watter dopluisagtiges (Hemiptera: Coccoidea in die neste in assosiasie met hierdie miere leef. Dopluise van drie families, naamlik die Pseudococcidae (witluise, Coccidae (sagtedopluise en Kerriidae (lakdopluise is in die neste gevind, almal bekend daarvoor dat hulle heuningdou afskei. Hierdie mutualistiese verhouding tussen die miere en dopluise, bekend as mirmekofilie, is fakultatief van aard. Die wipstertmier blyk ook nie spesifiek te wees wat betref die plant waarop hulle nes maak nie.

History of the Waterways Experiment Station

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1968-06-01

United Fund, Cancer , Heart, etc . , is also provided. In Jackson, WES employees serve as members of the Civil War Round Table of Missis- sippi, the...but problems still remained. The economic depression of the thirties was now in full swing, and by law there was a prohibition against making new...34· ..... CT ,_, c .... URIJ(JUJ!U &RAf£W fLUIBI.f fA’YfMfNl MAMa ; l f .,..,., CO..J 8 G-Nit.·if) ""’’ PUNT AQ •• I(H CtOlbe’f’ WHO! A.Lftllwl•,t ""’ Olitl

Spinal motor neuron involvement in a patient with homozygous PRUNE mutation.

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Iacomino, Michele; Fiorillo, Chiara; Torella, Annalaura; Severino, Mariasavina; Broda, Paolo; Romano, Catia; Falsaperla, Raffaele; Pozzolini, Giulia; Minetti, Carlo; Striano, Pasquale; Nigro, Vincenzo; Zara, Federico

2018-05-01

In the last few years, whole exome sequencing (WES) allowed the identification of PRUNE mutations in patients featuring a complex neurological phenotype characterized by severe neurodevelopmental delay, microcephaly, epilepsy, optic atrophy, and brain or cerebellar atrophy. We describe an additional patient with homozygous PRUNE mutation who presented with spinal muscular atrophy phenotype, in addition to the already known brain developmental disorder. This novel feature expands the clinical consequences of PRUNE mutations and allow to converge PRUNE syndrome with previous descriptions of neurodevelopmental/neurodegenerative disorders linked to altered microtubule dynamics. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Whole-exome sequencing in amyotrophic lateral sclerosis suggests NEK1 is a risk gene in Chinese

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Jacob Gratten

2017-11-01

Full Text Available Abstract Background Amyotrophic lateral sclerosis (ALS is a progressive neurological disease characterised by the degeneration of motor neurons, which are responsible for voluntary movement. There remains limited understanding of disease aetiology, with median survival of ALS of three years and no effective treatment. Identifying genes that contribute to ALS susceptibility is an important step towards understanding aetiology. The vast majority of published human genetic studies, including for ALS, have used samples of European ancestry. The importance of trans-ethnic studies in human genetic studies is widely recognised, yet a dearth of studies of non-European ancestries remains. Here, we report analyses of novel whole-exome sequencing (WES data from Chinese ALS and control individuals. Methods WES data were generated for 610 ALS cases and 460 controls drawn from Chinese populations. We assessed evidence for an excess of rare damaging mutations at the gene level and the gene set level, considering only singleton variants filtered to have allele frequency less than 5 × 10–5 in reference databases. To meta-analyse our results with a published study of European ancestry, we used a Cochran–Mantel–Haenszel test to compare gene-level variant counts in cases vs controls. Results No gene passed the genome-wide significance threshold with ALS in Chinese samples alone. Combining rare variant counts in Chinese with those from the largest WES study of European ancestry resulted in three genes surpassing genome-wide significance: TBK1 (p = 8.3 × 10–12, SOD1 (p = 8.9 × 10–9 and NEK1 (p = 1.1 × 10–9. In the Chinese data alone, SOD1 and NEK1 were nominally significantly associated with ALS (p = 0.04 and p = 7 × 10–3, respectively and the case/control frequencies of rare coding variants in these genes were similar in Chinese and Europeans (SOD1: 1.5%/0.2% vs 0.9%/0.1%, NEK1 1.8%/0.4% vs 1.9%/0.8%. This

Intra-tumor genetic heterogeneity and mortality in head and neck cancer: analysis of data from the Cancer Genome Atlas.

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Mroz, Edmund A; Tward, Aaron D; Tward, Aaron M; Hammon, Rebecca J; Ren, Yin; Rocco, James W

2015-02-01

Although the involvement of intra-tumor genetic heterogeneity in tumor progression, treatment resistance, and metastasis is established, genetic heterogeneity is seldom examined in clinical trials or practice. Many studies of heterogeneity have had prespecified markers for tumor subpopulations, limiting their generalizability, or have involved massive efforts such as separate analysis of hundreds of individual cells, limiting their clinical use. We recently developed a general measure of intra-tumor genetic heterogeneity based on whole-exome sequencing (WES) of bulk tumor DNA, called mutant-allele tumor heterogeneity (MATH). Here, we examine data collected as part of a large, multi-institutional study to validate this measure and determine whether intra-tumor heterogeneity is itself related to mortality. Clinical and WES data were obtained from The Cancer Genome Atlas in October 2013 for 305 patients with head and neck squamous cell carcinoma (HNSCC), from 14 institutions. Initial pathologic diagnoses were between 1992 and 2011 (median, 2008). Median time to death for 131 deceased patients was 14 mo; median follow-up of living patients was 22 mo. Tumor MATH values were calculated from WES results. Despite the multiple head and neck tumor subsites and the variety of treatments, we found in this retrospective analysis a substantial relation of high MATH values to decreased overall survival (Cox proportional hazards analysis: hazard ratio for high/low heterogeneity, 2.2; 95% CI 1.4 to 3.3). This relation of intra-tumor heterogeneity to survival was not due to intra-tumor heterogeneity's associations with other clinical or molecular characteristics, including age, human papillomavirus status, tumor grade and TP53 mutation, and N classification. MATH improved prognostication over that provided by traditional clinical and molecular characteristics, maintained a significant relation to survival in multivariate analyses, and distinguished outcomes among patients having

Sequence variants of KHDRBS1 as high penetrance susceptibility risks for primary ovarian insufficiency by mis-regulating mRNA alternative splicing.

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Wang, Binbin; Li, Lin; Zhu, Ying; Zhang, Wei; Wang, Xi; Chen, Beili; Li, Tengyan; Pan, Hong; Wang, Jing; Kee, Kehkooi; Cao, Yunxia

2017-10-01

Does a novel heterozygous KHDRBS1 variant, identified using whole-exome sequencing (WES) in two patients with primary ovarian insufficiency (POI) in a pedigree, cause defects in mRNA alternative splicing? The heterozygous variant of KHDRBS1 was confirmed to cause defects in alternative splicing of many genes involved in DNA replication and repair. Studies in mice revealed that Khdrbs1 deficient females are subfertile, which manifests as delayed sexual maturity and significantly reduced numbers of secondary and pre-antral follicles. No mutation of KHDRBS1, however, has been reported in patients with POI. This genetic and functional study used WES to find putative mutations in a POI pedigree. Altogether, 215 idiopathic POI patients and 400 healthy controls were screened for KHDRBS1 mutations. Two POI patients were subjected to WES to identify sequence variants. Mutational analysis of the KHDRBS1 gene in 215 idiopathic POI patients and 400 healthy controls were performed. RNA-sequencing was carried out to find the mis-regulation of gene expression due to KHDRBS1 mutation. Bioinformatics was used to analyze the change in alternative splicing events. We identified a heterozygous mutation (c.460A > G, p.M154V) in KHDRBS1 in two patients. Further mutational analysis of 215 idiopathic POI patients with the KHDRBS1 gene found one heterozygous mutation (c.263C > T, p.P88L). We failed to find these two mutations in 400 healthy control women. Using RNA-sequencing, we found that the KGN cells expressing the M154V KHDRBS1 mutant had different expression of 66 genes compared with wild-type (WT) cells. Furthermore, 145 genes were alternatively spliced in M154V cells, and these genes were enriched for DNA replication and repair function, revealing a potential underlying mechanism of the pathology that leads to POI. Although the in vitro assays demonstrated the effect of the KHDRBS1 variant on alternative splicing, further studies are needed to validate the in vivo effects on germ

PSU/WES Interlaboratory Comparative Methodology Study of an Experimental Cementitious Repository Seal Material. Report 2. Final Results.

Science.gov (United States)

1982-03-01

SO3 t 1.90 2.05 1.86 Na 2OS 0.09 0.21 0.15 Na2 Ott 0.12 0.11 0.12 K 2OS 0.49 0.47 0.51 K 2Ott 0.47 0.46 0.51 TiO 2S 0.19 0.18 0.18 TiO 2tt 0.19 0.20...ths ctibatiti.basI o Ot 81 ialdepencdcni ivieasiarcinctits, is 0.004 jam tafrdClstancN from I to 5 pim and 0.CtO pmr tar distatices trunm 10 to 50 pmi

15 years of research on Oral-Facial-Digital syndromes: from 1 to 16 causal genes

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Bruel, Ange-Line; Franco, Brunella; Duffourd, Yannis; Thevenon, Julien; Jego, Laurence; Lopez, Estelle; Deleuze, Jean-François; Doummar, Diane; Giles, Rachel H.; Johnson, Colin A.; Huynen, Martijn A.; Chevrier, Véronique; Burglen, Lydie; Morleo, Manuela; Desguerres, Isabelle; Pierquin, Geneviève; Doray, Bérénice; Gilbert-Dussardier, Brigitte; Reversade, Bruno; Steichen-Gersdorf, Elisabeth; Baumann, Clarisse; Panigrahi, Inusha; Fargeot-Espaliat, Anne; Dieux, Anne; David, Albert; Goldenberg, Alice; Bongers, Ernie; Gaillard, Dominique; Argente, Jesús; Aral, Bernard; Gigot, Nadège; St-Onge, Judith; Birnbaum, Daniel; Phadke, Shubha R.; Cormier-Daire, Valérie; Eguether, Thibaut; Pazour, Gregory J.; Herranz-Pérez, Vicente; Lee, Jaclyn S.; Pasquier, Laurent; Loget, Philippe; Saunier, Sophie; Mégarbané, André; Rosnet, Olivier; Leroux, Michel R.; Wallingford, John B.; Blacque, Oliver E.; Nachury, Maxence V.; Attie-Bitach, Tania; Rivière, Jean-Baptiste; Faivre, Laurence; Thauvin-Robinet, Christel

2017-01-01

Oral-facial-digital syndromes (OFDS) gather rare genetic disorders characterized by facial, oral and digital abnormalities associated with a wide range of additional features (polycystic kidney disease, cerebral malformations and several others) to delineate a growing list of OFD subtypes. The most frequent, OFD type I, is caused by a heterozygous mutation in the OFD1 gene encoding a centrosomal protein. The wide clinical heterogeneity of OFDS suggests the involvement of other ciliary genes. For 15 years, we have aimed to identify the molecular bases of OFDS. This effort has been greatly helped by the recent development of whole exome sequencing (WES). Here, we present all our published and unpublished results for WES in 24 OFDS cases. We identified causal variants in five new genes (C2CD3, TMEM107, INTU, KIAA0753, IFT57) and related the clinical spectrum of four genes in other ciliopathies (C5orf42, TMEM138, TMEM231, WDPCP) to OFDS. Mutations were also detected in two genes previously implicated in OFDS. Functional studies revealed the involvement of centriole elongation, transition zone and intraflagellar transport defects in OFDS, thus characterizing three ciliary protein modules: the complex KIAA0753-FOPNL-OFD1, a regulator of centriole elongation; the MKS module, a major component of the transition zone; and the CPLANE complex necessary for IFT-A assembly. OFDS now appear to be a distinct subgroup of ciliopathies with wide heterogeneity, which makes the initial classification obsolete. A clinical classification restricted to the three frequent/well-delineated subtypes could be proposed, and for patients who do not fit one of these 3 main subtypes, a further classification could be based on the genotype. PMID:28289185

Quality assurance plan for placement of cold-cap grout, demonstration vault, Hanford Grout Vault Program. Final report

Energy Technology Data Exchange (ETDEWEB)

Harrington, P.T.; Wakeley, L.D.; Ernzen, J.J.; Walley, D.M.

1992-08-01

During FY 91, the U.S. Army Engineer Waterways Experiment Station (WES) developed a grout to be used as a cold cap, a nonradioactive layer, between the solidified waste and the cover blocks of a demonstration waste disposal vault at the U.S. Department of Energy Hanford Facility. This document recommends requirements for a quality assurance (QA) plan for field mixing and placing of the cold-cap grout during final closure of the demonstration vault. Preplacement activities emphasize selection and testing of materials that will match the performance of materials used in the WES grout. Materials sources and applicable American Society of Testing and Materials, American Concrete Institute, and American Petroleum Institute specifications and requirements are provided. Archiving of physical samples of materials is essential, in addition to careful maintenance of test reports and laboratory data. Full-scale field trial mixing and a detailed preconstruction conference are recommended. Placement activities focus on production and placement of a grout that remains sufficiently constant throughout all batches and meets performance requirements. QA activities must be coordinated between the batch plant and delivery site. Recommended sampling during placement includes cylinders cast for subsequent tests of compressive strength and for nondestructive evaluation and prisms cast for monitoring volume stability. A minimum of two lifts is recommended. Postplacement activities include long-term monitoring of the properties of grout specimens cast during placement. Minimum testing of cylinders includes pulse velocity, fundamental frequency, and unconfined compressive strength. Monitoring characteristics of the microstructure also are recommended. The QA plan should designate an organization to have responsibility for maintaining complete records, reports, and archived samples, including details of deviations from plans written before field placement.

Germline CDKN2A/P16INK4A mutations contribute to genetic determinism of sarcoma.

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Jouenne, Fanélie; Chauvot de Beauchene, Isaure; Bollaert, Emeline; Avril, Marie-Françoise; Caron, Olivier; Ingster, Olivier; Lecesne, Axel; Benusiglio, Patrick; Terrier, Philippe; Caumette, Vincent; Pissaloux, Daniel; de la Fouchardière, Arnaud; Cabaret, Odile; N'Diaye, Birama; Velghe, Amélie; Bougeard, Gaelle; Mann, Graham J; Koscielny, Serge; Barrett, Jennifer H; Harland, Mark; Newton-Bishop, Julia; Gruis, Nelleke; Van Doorn, Remco; Gauthier-Villars, Marion; Pierron, Gaelle; Stoppa-Lyonnet, Dominique; Coupier, Isabelle; Guimbaud, Rosine; Delnatte, Capucine; Scoazec, Jean-Yves; Eggermont, Alexander M; Feunteun, Jean; Tchertanov, Luba; Demoulin, Jean-Baptiste; Frebourg, Thierry; Bressac-de Paillerets, Brigitte

2017-09-01

Sarcomas are rare mesenchymal malignancies whose pathogenesis is poorly understood; both environmental and genetic risk factors could contribute to their aetiology. We performed whole-exome sequencing (WES) in a familial aggregation of three individuals affected with soft-tissue sarcoma (STS) without TP53 mutation (Li-Fraumeni-like, LFL) and found a shared pathogenic mutation in CDKN2A tumour suppressor gene. We searched for individuals with sarcoma among 474 melanoma-prone families with a CDKN2A -/+ genotype and for CDKN2A mutations in 190 TP53 -negative LFL families where the index case was a sarcoma. Including the initial family, eight independent sarcoma cases carried a germline mutation in the CDKN2A /p16 INK4A gene. In five out of seven formalin-fixed paraffin-embedded sarcomas, heterozygosity was lost at germline CDKN2A mutations sites demonstrating complete loss of function. As sarcomas are rare in CDKN2A /p16 INK4A carriers, we searched in constitutional WES of nine carriers for potential modifying rare variants and identified three in platelet-derived growth factor receptor ( PDGFRA ) gene. Molecular modelling showed that two never-described variants could impact the PDGFRA extracellular domain structure. Germline mutations in CDKN2A /P16 INK4A , a gene known to predispose to hereditary melanoma, pancreatic cancer and tobacco-related cancers, account also for a subset of hereditary sarcoma. In addition, we identified PDGFRA as a candidate modifier gene. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Identification of the CFTR c.1666A>G Mutation in Hereditary Inclusion Body Myopathy Using Next-Generation Sequencing Analysis

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Yan Lu

2018-05-01

Full Text Available Hereditary inclusion body myopathy (HIBM is a rare autosomal recessive adult onset muscle disease which affects one to three individuals per million worldwide. This disease is autosomal dominant and occurs in adulthood. Our previous study reported a new subtype of HIBM linked to the susceptibility locus at 7q22.1-31.1. The present study is aimed to identify the candidate gene responsible for the phenotype in HIBM pedigree. After multipoint linkage analysis, we performed targeted capture sequencing on 16 members and whole-exome sequencing (WES on 5 members. Bioinformatics filtering was performed to prioritize the candidate pathogenic gene variants, which were further genotyped by Sanger sequencing. Our results showed that the highest peak of LOD score (4.70 was on chromosome 7q22.1-31.1.We identified 2 and 22 candidates using targeted capture sequencing and WES respectively, only one of which as CFTRc.1666A>G mutation was well cosegregated with the HIBM phenotype. Using transcriptome analysis, we did not detect the differences of CFTR's mRNA expression in the proband compared with healthy members. Due to low incidence of HIBM and there is no other pedigree to assess, mutation was detected in three patients with duchenne muscular dystrophyn (DMD and five patients with limb-girdle muscular dystrophy (LGMD. And we found that the frequency of mutation detected in DMD and LGMD patients was higher than that of being expected in normal population. We suggested that the CFTRc.1666A>G may be a candidate marker which has strong genetic linkage with the causative gene in the HIBM family.

De Novo Insertions and Deletions of Predominantly Paternal Origin Are Associated with Autism Spectrum Disorder

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Shan Dong

2014-10-01

Full Text Available Summary: Whole-exome sequencing (WES studies have demonstrated the contribution of de novo loss-of-function single-nucleotide variants (SNVs to autism spectrum disorder (ASD. However, challenges in the reliable detection of de novo insertions and deletions (indels have limited inclusion of these variants in prior analyses. By applying a robust indel detection method to WES data from 787 ASD families (2,963 individuals, we demonstrate that de novo frameshift indels contribute to ASD risk (OR = 1.6; 95% CI = 1.0–2.7; p = 0.03, are more common in female probands (p = 0.02, are enriched among genes encoding FMRP targets (p = 6 × 10−9, and arise predominantly on the paternal chromosome (p < 0.001. On the basis of mutation rates in probands versus unaffected siblings, we conclude that de novo frameshift indels contribute to risk in approximately 3% of individuals with ASD. Finally, by observing clustering of mutations in unrelated probands, we uncover two ASD-associated genes: KMT2E (MLL5, a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release. : Insertions and deletions (indels have proven especially difficult to detect in exome sequencing data. Dong et al. now identify indels in exome data for 787 autism spectrum disorder (ASD families. They demonstrate association between de novo indels that alter the reading frame and ASD. Furthermore, by observing clustering of indels in unrelated probands, they uncover two additional ASD-associated genes: KMT2E (MLL5, a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release.

Genetic Alterations in Essential Thrombocythemia Progression to Acute Myeloid Leukemia: A Case Series and Review of the Literature

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Jackline P. Ayres-Silva

2018-02-01

Full Text Available The genetic events associated with transformation of myeloproliferative neoplasms (MPNs to secondary acute myeloid leukemia (sAML, particularly in the subgroup of essential thrombocythemia (ET patients, remain incompletely understood. Deep studies using high-throughput methods might lead to a better understanding of genetic landscape of ET patients who transformed to sAML. We performed array-based comparative genomic hybridization (aCGH and whole exome sequencing (WES to analyze paired samples from ET and sAML phases. We investigated five patients with previous history of MPN, which four had initial diagnosis of ET (one case harboring JAK2 p.Val617Phe and the remaining three CALR type II p.Lys385fs*47, and one was diagnosed with MPN/myelodysplastic syndrome with thrombocytosis (SF3B1 p.Lys700Glu. All were homogeneously treated with hydroxyurea, but subsequently transformed to sAML (mean time of 6 years/median of 4 years to transformation. Two of them have chromosomal abnormalities, and both acquire 2p gain and 5q deletion at sAML stage. The molecular mechanisms associated with leukemic progression in MPN patients are not clear. Our WES data showed TP53 alterations recurrently observed as mutations (missense and frameshift and monoallelic loss. On the other hand, aCGH showed novel chromosome abnormalities (+2p and del5q potentially associated with disease progression. The results reported here add valuable information to the still fragmented molecular basis of ET to sAML evolution. Further studies are necessary to identify minimal deleted/amplified region and genes relevant to sAML transformation.

Numerous BAF complex genes are mutated in Coffin-Siris syndrome.

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Miyake, Noriko; Tsurusaki, Yoshinori; Matsumoto, Naomichi

2014-09-01

Coffin-Siris syndrome (CSS; OMIM#135900) is a rare congenital anomaly syndrome characterized by intellectual disability, coarse face, hypertrichosis, and absence/hypoplasia of the fifth digits' nails. As the majority of patients are sporadic, an autosomal dominant inheritance model has been postulated. Recently, whole exome sequencing (WES) emerged as a comprehensive analytical method for rare variants. We applied WES on five CSS patients and found two de novo mutations in SMARCB1. SMARCB1 was completely sequenced in 23 CSS patients and the mutations were found in two more patients. As SMARCB1 encodes a subunit of the BAF complex functioning as a chromatin remodeling factor, mutations in 15 other subunit genes may cause CSS and thus were analyzed in 23 CSS patients. We identified heterozygous mutations in either of six genes (SMARCA4, SMARCB1, SMARCA2, SMARCE1, ARID1A, and ARID1B) in 20 out of 23 CSS patients. The patient with a SMARCA2 mutation was re-evaluated and identified as having Nicolaides-Baraitser syndrome (OMIM#601358), which is similar to but different from CSS. Additionally, 49 more CSS patients were analyzed as a second cohort. Together with the first cohort, 37 out of 71 (22 plus 49) patients were found to have a mutation in either one of five BAF complex genes. Furthermore, two CSS patients were reported to have a PHF6 abnormality, which can also cause Borjeson-Forssman-Lehmann syndrome (OMIM#301900), an X-linked intellectual disability syndrome with epilepsy and endocrine abnormalities. The current list of mutated genes in CSS is far from being complete and analysis of more patients is required. © 2014 Wiley Periodicals, Inc.

Homozygous loss of function BRCA1 variant causing a Fanconi-anemia-like phenotype, a clinical report and review of previous patients.

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Freire, Bruna L; Homma, Thais K; Funari, Mariana F A; Lerario, Antônio M; Leal, Aline M; Velloso, Elvira D R P; Malaquias, Alexsandra C; Jorge, Alexander A L

2018-03-01

Fanconi Anemia (FA) is a rare and heterogeneous genetic syndrome. It is associated with short stature, bone marrow failure, high predisposition to cancer, microcephaly and congenital malformation. Many genes have been associated with FA. Previously, two adult patients with biallelic pathogenic variant in Breast Cancer 1 gene (BRCA1) had been identified in Fanconi Anemia-like condition. The proband was a 2.5 year-old girl with severe short stature, microcephaly, neurodevelopmental delay, congenital heart disease and dysmorphic features. Her parents were third degree cousins. Routine screening tests for short stature was normal. We conducted whole exome sequencing (WES) of the proband and used an analysis pipeline to identify rare nonsynonymous genetic variants that cause short stature. We identified a homozygous loss-of-function BRCA1 mutation (c.2709T > A; p. Cys903*), which promotes the loss of critical domains of the protein. Cytogenetic study with DEB showed an increased chromosomal breakage. We screened heterozygous parents of the index case for cancer and we detected, in her mother, a metastatic adenocarcinoma in an axillar lymph node with probable primary site in the breast. It is possible to consolidate the FA-like phenotype associated with biallelic loss-of-function BRCA1, characterized by microcephaly, short stature, developmental delay, dysmorphic face features and cancer predisposition. In our case, the WES allowed to establish the genetic cause of short stature in the context of a chromosome instability syndrome. An identification of BRCA1 mutations in our patient allowed precise genetic counseling and also triggered cancer screening for the patient and her family members. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

CEP250 mutations associated with mild cone-rod dystrophy and sensorineural hearing loss in a Japanese family.

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Kubota, Daiki; Gocho, Kiyoko; Kikuchi, Sachiko; Akeo, Keiichiro; Miura, Masahiro; Yamaki, Kunihiko; Takahashi, Hiroshi; Kameya, Shuhei

2018-05-02

CEP250 encodes the C-Nap1 protein which belongs to the CEP family of proteins. C-Nap1 has been reported to be expressed in the photoreceptor cilia and is known to interact with other ciliary proteins. Mutations of CEP250 cause atypical Usher syndrome which is characterized by early-onset sensorineural hearing loss (SNHL) and a relatively mild retinitis pigmentosa. This study tested the hypothesis that the mild cone-rod dystrophy (CRD) and SNHL in a non-consanguineous Japanese family was caused by CEP250 mutations. Detailed ophthalmic and auditory examinations were performed on the proband and her family members. Whole exome sequencing (WES) was used on the DNA obtained from the proband. Electrophysiological analysis revealed a mild CRD in two family members. Adaptive optics (AO) imaging showed reduced cone density around the fovea. Auditory examinations showed a slight SNHL in both patients. WES of the proband identified compound heterozygous variants c.361C>T, p.R121*, and c.562C>T, p.R188* in CEP250. The variants were found to co-segregate with the disease in five members of the family. The variants of CEP250 are both null variants and according to American College of Medical Genetics and Genomics (ACMG) standards and guideline, these variants are classified into the very strong category (PVS1). The criteria for both alleles will be pathogenic. Our data indicate that mutations of CEP250 can cause mild CRD and SNHL in Japanese patients. Because the ophthalmological phenotypes were very mild, high-resolution retinal imaging analysis, such as AO, will be helpful in diagnosing CEP250-associated disease.

Whole exome sequencing identified 1 base pair novel deletion in BCL2-associated athanogene 3 (BAG3) gene associated with severe dilated cardiomyopathy (DCM) requiring heart transplant in multiple family members.

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Rafiq, Muhammad Arshad; Chaudhry, Ayeshah; Care, Melanie; Spears, Danna A; Morel, Chantal F; Hamilton, Robert M

2017-03-01

Dilated cardiomyopathy (DCM) is characterized by dilation and impaired contraction of the left ventricle or both ventricles. Among hereditary DCM, the genetic causes are heterogeneous, and include mutations encoding cytoskeletal, nucleoskeletal, mitochondrial, and calcium-handling proteins. We report three severely affected males, in a four-generation pedigree, with DCM phenotype who underwent cardiac transplant. Cardiomegaly with marked biventricular dilation and fibrosis were noticeable histopathological findings. The affected males had tested negative on a 46-gene pancardiomyopathy panel. Whole Exome Sequencing (WES) was performed to reveal mutation in the gene responsible in generation of DCM phenotypes. The 1-bp (Chr10:121435979delC; c.913delC) novel heterozygous deletion in exon 4 of BAG3, was identified in three affected males, resulted in frame-shift and a premature termination codon (p.Met306-Stop) producing a truncated BAG3 protein lacking functionally important PXXP and BAG domains. WES data were further utilized to map 10 SNP markers around the discovered mutation to generate shared disease haplotype in all affected individuals encompassing 11 Mb on 10q25.3-26.2 harboring BAG3. Finally genotypes were inferred for the unavailable/deceased individuals in the pedigrees. Here we propose that Chr10:121435979delC in BAG3 is a causal mutation in these subjects. Our and earlier studies indicate that BAG3 mutations are associated with DCM phenotypes. BAG3 should be added to cardiomyopathy gene panels for screening of DCM patients, and patients previously considered gene elusive should undergo sequencing of the BAG3 gene. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

From Pericles to Plato – from democratic political praxis to totalitarian political philosophy

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Øjvind Larsen

2012-03-01

Full Text Available Plato is normally taken as one of the founders of Western political philosophy, not at least with his Republic. Here, he constructs a hierarchy of forms of governments, beginning with aristocracy at the top as a critical standard for the other forms of governments, and proceeding through timocracy and oligarchy to democracy and tyranny at the bottom. Following Karl Popper, the paper argues that Plato’s is a totalitarian philosophy that emphasizes the similarities between democracy and tyranny, which it considers to be the two worst forms of government. Plato’s denigration of democracy has dominated the tradition of political philosophy until recent times. This paper, however, shows that political philosophy in fact originates in democracy, especially as developed by the sophists and that philosophy is only a form of sophism with a similar origin in ancient Greek democracy. A discussion of Pericles’ funeral oration is used to show that Pericles presented a democratic political philosophy that can serve as a counterpoint to Plato’s political philosophy in the Republic.

Dictator Perpetuus: Julius Caesar--did he have seizures? If so, what was the etiology?

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Hughes, John R

2004-10-01

The "Dictator Perpetuus" of the Roman Empire, the great Julius Caesar, was not the one for whom the well-known cesarean operation was named; instead, this term is derived from a Latin word meaning "to cut." Caesar likely had epilepsy on the basis of four attacks that were probably complex partial seizures: (1) while listening to an oration by Cicero, (2) in the Senate while being offered the Emperor's Crown, and in military campaigns, (3) near Thapsus (North Africa) and (4) Corduba (Spain). Also, it is possible that he had absence attacks as a child and as a teenager. His son, Caesarion, by Queen Cleopatra, likely had seizures as a child, but the evidence is only suggestive. His great-great-great grandnephews Caligula and Britannicus also had seizures. The etiology of these seizures in this Julio-Claudian family was most likely through inheritance, with the possibility of sudden unexpected death in epilepsy (SUDEP) in his great grandfather and also his father. Our best evidence comes from the ancient sources of Suetonius, Plutarch, Pliny, and Appianus.

Algumas anedotas sobre Demóstenes: uma releitura

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Maddalena Vallozza

2013-06-01

Full Text Available Muitas das anedotas sobre Demóstenes estão relacionados a seus problemas de voz e a suas dificuldades no momento da hypokrisis. Eu proponho uma reinterpretação das páginas em que eles nos são transmitidos: de Quintiliano (11, 3, a principal testemunha, a Cícero (Orator 26 e 56-58, Brutus 142, De Oratore I 261 e III 213, do autor da seção sobre Demóstenes nas Vidas dos Dez Oradores (844 d-845 b à Vida de Demóstene, de Plutarco. Com base nisso, particularmente graças a Plutarco, que cita Hermipo e Demétrio de Fáleros, é possível formular a hipótese de que a tradição nasceu no Perípato, na área de interesses pela hypokrisis que demonstram o perdido Perì hypokríseos de Teofrasto e os fragmentos da Retórica de Demétrio de Fáleros.

La proyección oratoria de Ernesto Guevara de la Serna Ernesto Guevara de la Serna’s oratorical projection

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Zenaida Vicente Portales

2011-08-01

Full Text Available Es incuestionable el legado de la oratoria de Ernesto Guevara de la Serna para la construcción del socialismo en Cuba. Ello se confirma en este trabajo que ofrece un acercamiento a la proyección del Che como orador político: el carácter histórico, reflexivo y didáctico de los discursos pronunciados por él en diferentes escenarios, fundamentalmente de los dirigidos al pueblo en la etapa que reclamaba el contacto y el diálogo de los dirigentes con la masa, ávida de compenetrarse con la nueva ideología revolucionaria.Ernesto Guevara de la Serna’s oratorical legacy is unquestionable to build socialism in Cuba. This paper confirms this statement by approaching Che’s projection as political orator: the historical, reflexive, didactical character of his speeches given to the people in diverse sceneries, especially in a period demanding contact between leaders and masses eager to identify closely with the new revolutionary ideology in power.

The Asian Values in Singapore`s Context of Use. The Curbsides of the Singapore`s Model of Democracy

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Bianca Berna

2013-11-01

Full Text Available Out of a sense of nationhood or out of mere circumstantial and specific relatings to a national context, it is altogether visible that anti-universalist debate is making headway in international relations, in cultural studies and in the political science, if we are to classify a broader consultation of events.This article is aimed at presenting how the Western ideas can be seen, in examination, as artificial structures, in the national context of Asia. The Asian Values are a very interesting evaluative specimen of the anti-universalist orations. In the case of many Asian states, they created settled forms of government, having an especial adaptation with the originating incidents that were their birthplace. With the inward of these units of contextualization, we will turn to the conferral of the Singapore democracy model and to its germane bloc and bond with the Asian Values. We will interrelate a personal conspectus regarding the correctness of the seal of fastening between the Asian Values and Singapore`s democracy model.

DISCURSO POLÍTICO E FALA PÚBLICA: UM DIÁLOGO ENTRE HANNAH ARENDT E MARCO TÚLIO CÍCERO

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Mariana de Mattos Rubiano

2014-10-01

Full Text Available A ascensão do totalitarismo provocou Hannah Arendt a pensar sobre as atividades na esfera pública. Segundo ela, historicamente, as atividades públicas estavam relacionadas com a liberdade, principalmente na Antiguidade. No entanto, a dominação totalitária mudou essa relação. A ação livre e o discurso político na esfera pública foram substituídos pelo movimento de massas, doutrinação e propaganda. Este artigo visa a compreender a diferença enfatizada por Arendt entre a fala pública ligada à dominação e o discurso político. Em primeiro lugar, este texto trata do conceito arendtiano de discurso. A fim de esclarecer tal conceito, o pensamento de Cícero sobre oratória será apresentado. A terceira parte discute a fala pública e a propaganda durante o totalitarismo. Por último, o texto compara o caráter do discurso político e da fala pública no contexto totalitário.

"WE ARE ALL IN THE SAME BOAT NOW" PROVERBIAL RHETORIC IN THE CHURCHILL-ROOSEVELT CORRESPONDENCE

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Wolfgang Mieder

2006-06-01

Full Text Available Both Winston S. Churchill (1874-1965 and Franklin D. Roosevelt (1 882-1945 were masters of the English language and effective orators, rallying their people through word and deed to fight as allies against the dictatorial powers during the Second World War. Their public speeches and interviews are replete with proverbs, proverbial expressions, and other phraseologisms. This is also true for their private and secretive letters, messages, memoranda, and telegrams, as can be seen from the materials that Warren F. Kimball edited in the three volumes of Churchill & Roosevelt: The Complete Correspondence (Princeton, NJ: Princeton University Press, 1984. The proverbial language, especially metaphorical texts referring to the body, animals, and the military, gives their important communications a lively and humane flavor that illustrates their deep friendship, trust, and support of each other. Frequently used as metaphorical arguments, these proverbial interjections into an otherwise factual epistolary exchange from 1933 to 1945 bear witness to the determination of these two world leaders to win the struggle for a free world.

Delle maniere inusuali nel trattare argomenti insoliti - Unusual ways to treat unusual arguments

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Antonio Luigi Palmisano

2012-10-01

Full Text Available All those social and political projects aiming at the promotion of justice and morality have been labelled “utopia” – even if they will not be realized – after the publication of Thomas More’s work. But a specialist of rhetoric, and a fortiori an able rhetorician such as More, connected the word topoi first of all with the meaning loci communes, just like Aristotle, Cicerone and Boezio: recurrent arguments, organized in a conventional shape, even stereotyped and functional to the construction of the oration. The persuasive tale realized by the rhetorician. And the island of More, to More’s own eyes and to the eyes and ears of his readers and listeners, was anything but a recurrent argument or stereotype, and still less an dialectic argumentation: it actually was a “non-topos”. The article also suggests that it is essentially thanks to its non dialectic style of argumentation that the actual history of utopia and utopian thought settled between philosophy and fiction, theology and politology, economy and sociology, science and science fiction.

Characterization of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next generation sequencing study

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Mirzaa, Ghayda; Conti, Valerio; Timms, Andrew E.; Smyser, Christopher D.; Ahmed, Sarah; Carter, Melissa; Barnett, Sarah; Hufnagel, Robert B.; Goldstein, Amy; Narumi-Kishimoto, Yoko; Olds, Carissa; Collins, Sarah; Johnston, Kathreen; Deleuze, Jean-François; Nitschké, Patrick; Friend, Kathryn; Harris, Catharine; Goetsch, Allison; Martin, Beth; Boyle, Evan August; Parrini, Elena; Mei, Davide; Tattini, Lorenzo; Slavotinek, Anne; Blair, Ed; Barnett, Christopher; Shendure, Jay; Chelly, Jamel; Dobyns, William B.; Guerrini, Renzo

2015-01-01

SUMMARY Background Bilateral perisylvian polymicrogyria (BPP), the most common form of regional polymicrogyria, causes the congenital bilateral perisylvian syndrome, featuring oromotor dysfunction, cognitive impairment and epilepsy. BPP is etiologically heterogeneous, but only a few genetic causes have been reported. The aim of this study was to identify additional genetic etiologies of BPP and delineate their frequency in this patient population. Methods We performed child-parent (trio)-based whole exome sequencing (WES) on eight children with BPP. Following the identification of mosaic PIK3R2 mutations in two of these eight children, we performed targeted screening of PIK3R2 in a cohort of 118 children with BPP who were ascertained from 1980 until 2015 using two methods. First, we performed targeted sequencing of the entire PIK3R2 gene by single molecule molecular inversion probes (smMIPs) on 38 patients with BPP with normal-large head size. Second, we performed amplicon sequencing of the recurrent PIK3R2 mutation (p.Gly373Arg) on 80 children with various types of polymicrogyria including BPP. One additional patient underwent clinical WES independently, and was included in this study given the phenotypic similarity to our cohort. All patients included in this study were children (BPP. Of the 38 patients with BPP and normal-large head size who underwent targeted next generation sequencing by smMIPs, we identified constitutional and mosaic PIK3R2 mutations in 17 additional children. In parallel, one patient was found to have the recurrent PIK3R2 mutation by clinical WES. Seven patients had BPP alone, and 13 had BPP in association with features of the megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH). Nineteen patients had the same mutation (Gly373Arg), and one had a nearby missense mutation (p.Lys376Glu). Across the entire cohort, mutations were constitutional in 12 and mosaic in eight patients. Among mosaic patients, we observed substantial

Genomic landscape of ovarian clear cell carcinoma via whole exome sequencing.

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Kim, Se Ik; Lee, Ji Won; Lee, Maria; Kim, Hee Seung; Chung, Hyun Hoon; Kim, Jae-Weon; Park, Noh Hyun; Song, Yong-Sang; Seo, Jeong-Sun

2018-02-01

To analyze whole exome sequencing (WES) data on ovarian clear cell carcinoma (OCCC) in Korean patients via the technique of next generation sequencing (NGS). Genomic profiles were compared between endometriosis-associated OCCC (EMS-OCCC) and Non-EMS-OCCC. We used serum samples and cancer tissues, stored at the Seoul National University Hospital Human Biobank, that were initially collected from women diagnosed with OCCC between 2012 and 2016. In total, 15 patients were enrolled: 5 with pathologically confirmed EMS-OCCC and 10 with Non-EMS-OCCC. We performed NGS WES on 15 fresh frozen OCCC tissues and matched serum samples, enabling comprehensive genomic characterization of OCCC. OCCC was characterized by complex genomic alterations, with a median of 178 exonic mutations (range, 111-25,798) and a median of 343 somatic copy number variations (range, 43-1,820) per tumor sample. In all, 54 somatic mutations were discovered across 14 genes, including PIK3CA (40%), ARID1A (40%), and KRAS (20%) in the 15 Korean OCCCs. Copy number gains in NTRK1 (33%), MYC (40%), and GNAS (47%) and copy number losses in TET2 (73%), TSC1 (67%), BRCA2 (60%), and SMAD4 (47%) were frequent. The significantly altered pathways were associated with proliferation and survival (including the PI3K/AKT, TP53, and ERBB2 pathways) in 87% of OCCCs and with chromatin remodeling in 47% of OCCCs. No significant differences in frequencies of genetic alterations were detected between EMS-OCCC and Non-EMS-OCCC groups. We successfully characterized the genomic landscape of 15 Korean patients with OCCC. We identified potential therapeutic targets for the treatment of this malignancy. Copyright © 2017. Published by Elsevier Inc.

Analysis of rare, exonic variation amongst subjects with autism spectrum disorders and population controls.

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Li Liu

2013-04-01

Full Text Available We report on results from whole-exome sequencing (WES of 1,039 subjects diagnosed with autism spectrum disorders (ASD and 870 controls selected from the NIMH repository to be of similar ancestry to cases. The WES data came from two centers using different methods to produce sequence and to call variants from it. Therefore, an initial goal was to ensure the distribution of rare variation was similar for data from different centers. This proved straightforward by filtering called variants by fraction of missing data, read depth, and balance of alternative to reference reads. Results were evaluated using seven samples sequenced at both centers and by results from the association study. Next we addressed how the data and/or results from the centers should be combined. Gene-based analyses of association was an obvious choice, but should statistics for association be combined across centers (meta-analysis or should data be combined and then analyzed (mega-analysis? Because of the nature of many gene-based tests, we showed by theory and simulations that mega-analysis has better power than meta-analysis. Finally, before analyzing the data for association, we explored the impact of population structure on rare variant analysis in these data. Like other recent studies, we found evidence that population structure can confound case-control studies by the clustering of rare variants in ancestry space; yet, unlike some recent studies, for these data we found that principal component-based analyses were sufficient to control for ancestry and produce test statistics with appropriate distributions. After using a variety of gene-based tests and both meta- and mega-analysis, we found no new risk genes for ASD in this sample. Our results suggest that standard gene-based tests will require much larger samples of cases and controls before being effective for gene discovery, even for a disorder like ASD.

Bi-allelic Mutations in PKD1L1 Are Associated with Laterality Defects in Humans.

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Vetrini, Francesco; D'Alessandro, Lisa C A; Akdemir, Zeynep C; Braxton, Alicia; Azamian, Mahshid S; Eldomery, Mohammad K; Miller, Kathryn; Kois, Chelsea; Sack, Virginia; Shur, Natasha; Rijhsinghani, Asha; Chandarana, Jignesh; Ding, Yan; Holtzman, Judy; Jhangiani, Shalini N; Muzny, Donna M; Gibbs, Richard A; Eng, Christine M; Hanchard, Neil A; Harel, Tamar; Rosenfeld, Jill A; Belmont, John W; Lupski, James R; Yang, Yaping

2016-10-06

Disruption of the establishment of left-right (L-R) asymmetry leads to situs anomalies ranging from situs inversus totalis (SIT) to situs ambiguus (heterotaxy). The genetic causes of laterality defects in humans are highly heterogeneous. Via whole-exome sequencing (WES), we identified homozygous mutations in PKD1L1 from three affected individuals in two unrelated families. PKD1L1 encodes a polycystin-1-like protein and its loss of function is known to cause laterality defects in mouse and medaka fish models. Family 1 had one fetus and one deceased child with heterotaxy and complex congenital heart malformations. WES identified a homozygous splicing mutation, c.6473+2_6473+3delTG, which disrupts the invariant splice donor site in intron 42, in both affected individuals. In the second family, a homozygous c.5072G>C (p.Cys1691Ser) missense mutation was detected in an individual with SIT and congenital heart disease. The p.Cys1691Ser substitution affects a highly conserved cysteine residue and is predicted by molecular modeling to disrupt a disulfide bridge essential for the proper folding of the G protein-coupled receptor proteolytic site (GPS) motif. Damaging effects associated with substitutions of this conserved cysteine residue in the GPS motif have also been reported in other genes, namely GPR56, BAI3, and PKD1 in human and lat-1 in C. elegans, further supporting the likely pathogenicity of p.Cys1691Ser in PKD1L1. The identification of bi-allelic PKD1L1 mutations recapitulates previous findings regarding phenotypic consequences of loss of function of the orthologous genes in mice and medaka fish and further expands our understanding of genetic contributions to laterality defects in humans. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Integrated tumor and germline whole-exome sequencing identifies mutations in MAPK and PI3K pathway genes in an adolescent with rosette-forming glioneuronal tumor of the fourth ventricle

Science.gov (United States)

Lin, Frank Y.; Bergstrom, Katie; Person, Richard; Bavle, Abhishek; Ballester, Leomar Y.; Scollon, Sarah; Raesz-Martinez, Robin; Jea, Andrew; Birchansky, Sherri; Wheeler, David A.; Berg, Stacey L.; Chintagumpala, Murali M.; Adesina, Adekunle M.; Eng, Christine; Roy, Angshumoy; Plon, Sharon E.; Parsons, D. Williams

2016-01-01

The integration of genome-scale studies such as whole-exome sequencing (WES) into the clinical care of children with cancer has the potential to provide insight into the genetic basis of an individual's cancer with implications for clinical management. This report describes the results of clinical tumor and germline WES for a patient with a rare tumor diagnosis, rosette-forming glioneuronal tumor of the fourth ventricle (RGNT). Three pathogenic gene alterations with implications for clinical care were identified: somatic activating hotspot mutations in FGFR1 (p.N546K) and PIK3CA (p.H1047R) and a germline pathogenic variant in PTPN11 (p.N308S) diagnostic for Noonan syndrome. The molecular landscape of RGNT is not well-described, but these data are consistent with prior observations regarding the importance of the interconnected MAPK and PI3K/AKT/mTOR signaling pathways in this rare tumor. The co-occurrence of FGFR1, PIK3CA, and PTPN11 alterations provides further evidence for consideration of RGNT as a distinct molecular entity from pediatric low-grade gliomas and suggests potential therapeutic strategies for this patient in the event of tumor recurrence as novel agents targeting these pathways enter pediatric clinical trials. Although RGNT has not been definitively linked with cancer predisposition syndromes, two prior cases have been reported in patients with RASopathies (Noonan syndrome and neurofibromatosis type 1 [NF1]), providing an additional link between these tumors and the mitogen-activated protein kinase (MAPK) signaling pathway. In summary, this case provides an example of the potential for genome-scale sequencing technologies to provide insight into the biology of rare tumors and yield both tumor and germline results of potential relevance to patient care. PMID:27626068

Lightweight submersed 'Walking' NDE manipulators for PWR and BWR vessel weld inspection

International Nuclear Information System (INIS)

Saernmark, Ivan; Lenz, Herbert

2008-01-01

Three new manipulators developed by WesDyne TRC in Sweden have under the year 2007 performed three very successful inspections in the PWR reactor Ringhals 3 and the BWR reactors Ringhals 1 and Oskarshamn 1. The manipulator systems can be used to perform inspection of circumferential and vertical welds on the reactor pressure vessel, the core shroud, core shroud support in BWR reactors or vessel and core barrel welds in PWR reactors. Most other flat or curved surfaces can be inspected using the new concept through relatively simple mechanical reconfigurations of system modules. The first inspection was performed on the R3 PWR core barrel in June 2007 with a very good result. This Manipulator is designed for access in very narrow gaps and for the type of core barrels with a shield covering the whole area of the perimeter. The manipulator is attached to the inspection area by means of a new unique suction cup system. The current manipulators consist of a curved horizontal beam, with radius similar to the reactor vessel, and a straight vertical beam, forming a T-shaped structure. By alternating the application of suction cup pairs on the horizontal beam and the vertical beam and by driving the scanning motors, the manipulator performs an incremental translational movement upwards/downwards or from side to side. The principles of this system give a well defined and stable platform for global and local positioning accuracy. A combination of advanced sensor solutions provides accurate position information in the absence of other physical reference objects. The system is controlled by the new WesDyne TRC Motor Control Panel and software, the MCP is specifically designed for remote control of submersed manipulators using techniques for cable reduction

Lightweight submersed 'Walking' NDE manipulators for PWR and BWR vessel weld inspection

Energy Technology Data Exchange (ETDEWEB)

Saernmark, Ivan; Lenz, Herbert [WesDyne TRC AB, Stockholm (Sweden)

2008-04-15

Three new manipulators developed by WesDyne TRC in Sweden have under the year 2007 performed three very successful inspections in the PWR reactor Ringhals 3 and the BWR reactors Ringhals 1 and Oskarshamn 1. The manipulator systems can be used to perform inspection of circumferential and vertical welds on the reactor pressure vessel, the core shroud, core shroud support in BWR reactors or vessel and core barrel welds in PWR reactors. Most other flat or curved surfaces can be inspected using the new concept through relatively simple mechanical reconfigurations of system modules. The first inspection was performed on the R3 PWR core barrel in June 2007 with a very good result. This Manipulator is designed for access in very narrow gaps and for the type of core barrels with a shield covering the whole area of the perimeter. The manipulator is attached to the inspection area by means of a new unique suction cup system. The current manipulators consist of a curved horizontal beam, with radius similar to the reactor vessel, and a straight vertical beam, forming a T-shaped structure. By alternating the application of suction cup pairs on the horizontal beam and the vertical beam and by driving the scanning motors, the manipulator performs an incremental translational movement upwards/downwards or from side to side. The principles of this system give a well defined and stable platform for global and local positioning accuracy. A combination of advanced sensor solutions provides accurate position information in the absence of other physical reference objects. The system is controlled by the new WesDyne TRC Motor Control Panel and software, the MCP is specifically designed for remote control of submersed manipulators using techniques for cable reduction.

High-throughput genetic analysis in a cohort of patients with Ocular Developmental Anomalies

Directory of Open Access Journals (Sweden)

Suganya Kandeeban

2017-10-01

Full Text Available Anophthalmia and microphthalmia (A/M are developmental ocular malformations in which the eye fails to form or is smaller than normal with both genetic and environmental etiology. Microphthalmia is often associated with additional ocular anomalies, most commonly coloboma or cataract [1, 2]. A/M has a combined incidence between 1-3.2 cases per 10,000 live births in Caucasians [3, 4]. The spectrum of genetic abnormalities (chromosomal and molecular associated with these ocular developmental defects are being investigated in the current study. A detailed pedigree analysis and ophthalmic examination have been documented for the enrolled patients followed by blood collection and DNA extraction. The strategies for genetic analysis included chromosomal analysis by conventional and array based (affymetrix cytoscan HD array methods, targeted re-sequencing of the candidate genes and whole exome sequencing (WES in Illumina HiSEQ 2500. WES was done in families excluded for mutations in candidate genes. Twenty four samples (Microphthalmia (M-5, Anophthalmia (A-7,Coloboma-2, M&A-1, microphthalmia and coloboma / other ocular features-9 were initially analyzed using conventional Geimsa Trypsin Geimsa banding of which 4 samples revealed gross chromosomal aberrations (deletions in 3q26.3-28, 11p13 (N=2 and 11q23 regions. Targeted re sequencing of candidate genes showed mutations in CHX10, PAX6, FOXE3, ABCB6 and SHH genes in 6 samples. High throughput array based chromosomal analysis revealed aberrations in 4 samples (17q21dup (n=2, 8p11del (n=2. Overall, genetic alterations in known candidate genes are seen in 50% of the study subjects. Whole exome sequencing was performed in samples that were excluded for mutations in candidate genes and the results are discussed.

Creation of knock out and knock in mice by CRISPR/Cas9 to validate candidate genes for human male infertility, interest, difficulties and feasibility.

Science.gov (United States)

Kherraf, Zine-Eddine; Conne, Beatrice; Amiri-Yekta, Amir; Kent, Marie Christou; Coutton, Charles; Escoffier, Jessica; Nef, Serge; Arnoult, Christophe; Ray, Pierre F

2018-06-15

High throughput sequencing (HTS) and CRISPR/Cas9 are two recent technologies that are currently revolutionizing biological and clinical research. Both techniques are complementary as HTS permits to identify new genetic variants and genes involved in various pathologies and CRISPR/Cas9 permits to create animals or cell models to validate the effect of the identified variants, to characterize the pathogeny of the identified variants and the function of the genes of interest and ultimately to provide ways of correcting the molecular defects. We analyzed a cohort of 78 infertile men presenting with multiple morphological anomalies of the sperm flagella (MMAF), a severe form of male infertility. Using whole exome sequencing (WES), homozygous mutations in autosomal candidate genes were identified in 63% of the tested subjects. We decided to produce by CRISPR/cas9 four knock-out (KO) and one knock-in (KI) mouse lines to confirm these results and to increase our understanding of the physiopathology associated with these genetic variations. Overall 31% of the live pups obtained presented a mutational event in one of the targeted regions. All identified events were insertions or deletions localized near the PAM sequence. Surprisingly we observed a high rate of germline mosaicism as 30% of the F1 displayed a different mutation than the parental event characterized on somatic tissue (tail), indicating that CRISPR/Cas9 mutational events kept happening several cell divisions after the injection. Overall, we created mouse models for 5 distinct loci and in each case homozygous animals could be obtained in approximately 6 months. These results demonstrate that the combined use of WES and CRISPR/Cas9 is an efficient and timely strategy to identify and validate mutations responsible for infertility phenotypes in human. Copyright © 2018 Elsevier B.V. All rights reserved.

Exome sequencing of index patients with retinal dystrophies as a tool for molecular diagnosis.

Directory of Open Access Journals (Sweden)

Marta Corton

Full Text Available Retinal dystrophies (RD are a group of hereditary diseases that lead to debilitating visual impairment and are usually transmitted as a Mendelian trait. Pathogenic mutations can occur in any of the 100 or more disease genes identified so far, making molecular diagnosis a rather laborious process. In this work we explored the use of whole exome sequencing (WES as a tool for identification of RD mutations, with the aim of assessing its applicability in a diagnostic context.We ascertained 12 Spanish families with seemingly recessive RD. All of the index patients underwent mutational pre-screening by chip-based sequence hybridization and resulted to be negative for known RD mutations. With the exception of one pedigree, to simulate a standard diagnostic scenario we processed by WES only the DNA from the index patient of each family, followed by in silico data analysis. We successfully identified causative mutations in patients from 10 different families, which were later verified by Sanger sequencing and co-segregation analyses. Specifically, we detected pathogenic DNA variants (∼50% novel mutations in the genes RP1, USH2A, CNGB3, NMNAT1, CHM, and ABCA4, responsible for retinitis pigmentosa, Usher syndrome, achromatopsia, Leber congenital amaurosis, choroideremia, or recessive Stargardt/cone-rod dystrophy cases.Despite the absence of genetic information from other family members that could help excluding nonpathogenic DNA variants, we could detect causative mutations in a variety of genes known to represent a wide spectrum of clinical phenotypes in 83% of the patients analyzed. Considering the constant drop in costs for human exome sequencing and the relative simplicity of the analyses made, this technique could represent a valuable tool for molecular diagnostics or genetic research, even in cases for which no genotypes from family members are available.

A homozygous nonsense CEP250 mutation combined with a heterozygous nonsense C2orf71 mutation is associated with atypical Usher syndrome.

Science.gov (United States)

Khateb, Samer; Zelinger, Lina; Mizrahi-Meissonnier, Liliana; Ayuso, Carmen; Koenekoop, Robert K; Laxer, Uri; Gross, Menachem; Banin, Eyal; Sharon, Dror

2014-07-01

Usher syndrome (USH) is a heterogeneous group of inherited retinitis pigmentosa (RP) and sensorineural hearing loss (SNHL) caused by mutations in at least 12 genes. Our aim is to identify additional USH-related genes. Clinical examination included visual acuity test, funduscopy and electroretinography. Genetic analysis included homozygosity mapping and whole exome sequencing (WES). A combination of homozygosity mapping and WES in a large consanguineous family of Iranian Jewish origin revealed nonsense mutations in two ciliary genes: c.3289C>T (p.Q1097*) in C2orf71 and c.3463C>T (p.R1155*) in centrosome-associated protein CEP250 (C-Nap1). The latter has not been associated with any inherited disease and the c.3463C>T mutation was absent in control chromosomes. Patients who were double homozygotes had SNHL accompanied by early-onset and severe RP, while patients who were homozygous for the CEP250 mutation and carried a single mutant C2orf71 allele had SNHL with mild retinal degeneration. No ciliary structural abnormalities in the respiratory system were evident by electron microscopy analysis. CEP250 expression analysis of the mutant allele revealed the generation of a truncated protein lacking the NEK2-phosphorylation region. A homozygous nonsense CEP250 mutation, in combination with a heterozygous C2orf71 nonsense mutation, causes an atypical form of USH, characterised by early-onset SNHL and a relatively mild RP. The severe retinal involvement in the double homozygotes indicates an additive effect caused by nonsense mutations in genes encoding ciliary proteins. 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.

Analysis of Rare, Exonic Variation amongst Subjects with Autism Spectrum Disorders and Population Controls

Science.gov (United States)

Liu, Li; Sabo, Aniko; Neale, Benjamin M.; Nagaswamy, Uma; Stevens, Christine; Lim, Elaine; Bodea, Corneliu A.; Muzny, Donna; Reid, Jeffrey G.; Banks, Eric; Coon, Hillary; DePristo, Mark; Dinh, Huyen; Fennel, Tim; Flannick, Jason; Gabriel, Stacey; Garimella, Kiran; Gross, Shannon; Hawes, Alicia; Lewis, Lora; Makarov, Vladimir; Maguire, Jared; Newsham, Irene; Poplin, Ryan; Ripke, Stephan; Shakir, Khalid; Samocha, Kaitlin E.; Wu, Yuanqing; Boerwinkle, Eric; Buxbaum, Joseph D.; Cook, Edwin H.; Devlin, Bernie; Schellenberg, Gerard D.; Sutcliffe, James S.; Daly, Mark J.; Gibbs, Richard A.; Roeder, Kathryn

2013-01-01

We report on results from whole-exome sequencing (WES) of 1,039 subjects diagnosed with autism spectrum disorders (ASD) and 870 controls selected from the NIMH repository to be of similar ancestry to cases. The WES data came from two centers using different methods to produce sequence and to call variants from it. Therefore, an initial goal was to ensure the distribution of rare variation was similar for data from different centers. This proved straightforward by filtering called variants by fraction of missing data, read depth, and balance of alternative to reference reads. Results were evaluated using seven samples sequenced at both centers and by results from the association study. Next we addressed how the data and/or results from the centers should be combined. Gene-based analyses of association was an obvious choice, but should statistics for association be combined across centers (meta-analysis) or should data be combined and then analyzed (mega-analysis)? Because of the nature of many gene-based tests, we showed by theory and simulations that mega-analysis has better power than meta-analysis. Finally, before analyzing the data for association, we explored the impact of population structure on rare variant analysis in these data. Like other recent studies, we found evidence that population structure can confound case-control studies by the clustering of rare variants in ancestry space; yet, unlike some recent studies, for these data we found that principal component-based analyses were sufficient to control for ancestry and produce test statistics with appropriate distributions. After using a variety of gene-based tests and both meta- and mega-analysis, we found no new risk genes for ASD in this sample. Our results suggest that standard gene-based tests will require much larger samples of cases and controls before being effective for gene discovery, even for a disorder like ASD. PMID:23593035

A de novo whole gene deletion of XIAP detected by exome sequencing analysis in very early onset inflammatory bowel disease: a case report.

Science.gov (United States)

Kelsen, Judith R; Dawany, Noor; Martinez, Alejandro; Martinez, Alejuandro; Grochowski, Christopher M; Maurer, Kelly; Rappaport, Eric; Piccoli, David A; Baldassano, Robert N; Mamula, Petar; Sullivan, Kathleen E; Devoto, Marcella

2015-11-18

Children with very early-onset inflammatory bowel disease (VEO-IBD), those diagnosed at less than 5 years of age, are a unique population. A subset of these patients present with a distinct phenotype and more severe disease than older children and adults. Host genetics is thought to play a more prominent role in this young population, and monogenic defects in genes related to primary immunodeficiencies are responsible for the disease in a small subset of patients with VEO-IBD. We report a child who presented at 3 weeks of life with very early-onset inflammatory bowel disease (VEO-IBD). He had a complicated disease course and remained unresponsive to medical and surgical therapy. The refractory nature of his disease, together with his young age of presentation, prompted utilization of whole exome sequencing (WES) to detect an underlying monogenic primary immunodeficiency and potentially target therapy to the identified defect. Copy number variation analysis (CNV) was performed using the eXome-Hidden Markov Model. Whole exome sequencing revealed 1,380 nonsense and missense variants in the patient. Plausible candidate variants were not detected following analysis of filtered variants, therefore, we performed CNV analysis of the WES data, which led us to identify a de novo whole gene deletion in XIAP. This is the first reported whole gene deletion in XIAP, the causal gene responsible for XLP2 (X-linked lymphoproliferative Disease 2). XLP2 is a syndrome resulting in VEO-IBD and can increase susceptibility to hemophagocytic lymphohistocytosis (HLH). This identification allowed the patient to be referred for bone marrow transplantation, potentially curative for his disease and critical to prevent the catastrophic sequela of HLH. This illustrates the unique etiology of VEO-IBD, and the subsequent effects on therapeutic options. This cohort requires careful and thorough evaluation for monogenic defects and primary immunodeficiencies.

Understanding the El Niño-like Oceanic Response in the Tropical Pacific to Global Warming

Energy Technology Data Exchange (ETDEWEB)

Luo, Yiyong; Lu, Jian; Liu, Fukai; Liu, Wei

2015-10-10

The enhanced central and eastern Pacific SST warming and the associated ocean processes under global warming are investigated using the ocean component of the Community Earth System Model (CESM), Parallel Ocean Program version 2 (POP2). The tropical SST warming pattern in the coupled CESM can be faithfully reproduced by the POP2 forced with surface fluxes computed using the aerodynamic bulk formula. By prescribing the wind stress and/or wind speed through the bulk formula, the effects of wind stress change and/or the wind-evaporation-SST (WES) feedback are isolated and their linearity is evaluated in this ocean-alone setting. Result shows that, although the weakening of the equatorial easterlies contributes positively to the El Niño-like SST warming, 80% of which can be simulated by the POP2 without considering the effects of wind change in both mechanical and thermodynamic fluxes. This result points to the importance of the air-sea thermal interaction and the relative feebleness of the ocean dynamical process in the El Niño-like equatorial Pacific SST response to global warming. On the other hand, the wind stress change is found to play a dominant role in the oceanic response in the tropical Pacific, accounting for most of the changes in the equatorial ocean current system and thermal structures, including the weakening of the surface westward currents, the enhancement of the near-surface stratification and the shoaling of the equatorial thermocline. Interestingly, greenhouse gas warming in the absence of wind stress change and WES feedback also contributes substantially to the changes at the subsurface equatorial Pacific. Further, this warming impact can be largely replicated by an idealized ocean experiment forced by a uniform surface heat flux, whereby, arguably, a purest form of oceanic dynamical thermostat is revealed.

In situ, subsurface monitoring of vapor-phase TCE using fiber optics

International Nuclear Information System (INIS)

Rossabi, J.; Colston, B. Jr.; Brown, S.; Milanovich, F.; Lee, L.T. Jr.

1993-01-01

A vapor-phase, reagent-based, fiber optic trichloroethylene (TCE) sensor developed by Lawrence Livermore National Laboratory (LLNL) was demonstrated at the Savannah River Site (SRS) in two configurations. The first incorporated the sensor into a down-well instrument bounded by two inflatable packers capable of sealing an area for discrete depth analysis. The second involved an integration of the sensor into the probe tip of the Army Corps of Engineers Waterways Experiment Station (WES) cone penetrometry system. Discrete depth measurements of vapor-phase concentrations of TCE in the vadose zone were successfully made using both configurations. These measurements demonstrate the first successful in situ sensing (as opposed to sampling) of TCE at a field site

Drug resistance in colorectal cancer cell lines is partially associated with aneuploidy status in light of profiling gene expression

DEFF Research Database (Denmark)

Guo, Jiao; Xu, Shaohang; Huang, Xuanlin

2016-01-01

A priority in solving the problem of drug resistance is to understand the molecular mechanism of how a drug induces the resistance response within cells. Because many cancer cells exhibit chromosome aneuploidy, we explored whether changes of aneuploidy status result in drug resistance. Two typical...... colorectal cancer cells, HCT116 and LoVo, were cultured with the chemotherapeutic drugs irinotecan (SN38) or oxaliplatin (QxPt), and the non- and drug-resistant cell lines were selected. Whole exome sequencing (WES) was employed to evaluate the aneuploidy status of these cells, and RNAseq and LC-MS/MS were...... the aneuploidy status in cancer cells, which was partially associated with the acquired drug resistance....

Whole-exome sequencing identified a homozygous FNBP4 mutation in a family with a condition similar to microphthalmia with limb anomalies.

Science.gov (United States)

Kondo, Yukiko; Koshimizu, Eriko; Megarbane, Andre; Hamanoue, Haruka; Okada, Ippei; Nishiyama, Kiyomi; Kodera, Hirofumi; Miyatake, Satoko; Tsurusaki, Yoshinori; Nakashima, Mitsuko; Doi, Hiroshi; Miyake, Noriko; Saitsu, Hirotomo; Matsumoto, Naomichi

2013-07-01

Microphthalmia with limb anomalies (MLA), also known as Waardenburg anophthalmia syndrome or ophthalmoacromelic syndrome, is a rare autosomal recessive disorder. Recently, we and others successfully identified SMOC1 as the causative gene for MLA. However, there are several MLA families without SMOC1 abnormality, suggesting locus heterogeneity in MLA. We aimed to identify a pathogenic mutation in one Lebanese family having an MLA-like condition without SMOC1 mutation by whole-exome sequencing (WES) combined with homozygosity mapping. A c.683C>T (p.Thr228Met) in FNBP4 was found as a primary candidate, drawing the attention that FNBP4 and SMOC1 may potentially modulate BMP signaling. Copyright © 2013 Wiley Periodicals, Inc.

Ultrasonic testing of core baffle former bolts of the core tanks of pressurised water reactors; Ultraschallpruefung von Kernumfassungsschrauben der Kernbehaelter von Druckwasserreaktoren

Energy Technology Data Exchange (ETDEWEB)

Bies, Christian M.; Alaerts, Louis; Bonitz, Frank W. [Westinghouse Electric Germany GmbH, Mannheim (Germany); Devlin, Russell S.; Minogue, Patrick [WesDyne International, Madison, PA (United States)

2013-07-01

This article presents the MIDAS VI testing robot used by Westinghouse / WesDyne. This is a remotely operated underwater vehicle which positions ultrasonic probes under camera control. This vehicle makes it possible to substantially reduce the time required for setting up and preparing ultrasonic tests on core baffle former bolts. It has also accelerated the test procedure itself. Test methods have also been developed for bolt types which were hitherto considered incapable of being tested. One of these methods is based on a phased array probe. The article also reports on experiences gained over the course of years in testing core baffle former bolts in European nuclear power plants using the SUPREEM testing robot.

Effect of cerulenin on fatty acid composition and gene expression pattern of DHA-producing strain Colwellia psychrerythraea strain 34H.

Science.gov (United States)

Wan, Xia; Peng, Yun-Feng; Zhou, Xue-Rong; Gong, Yang-Min; Huang, Feng-Hong; Moncalián, Gabriel

2016-02-06

Colwellia psychrerythraea 34H is a psychrophilic bacterium able to produce docosahexaenoic acid (DHA). Polyketide synthase pathway is assumed to be responsible for DHA production in marine bacteria. Five pfa genes from strain 34H were confirmed to be responsible for DHA formation by heterogeneous expression in Escherichia coli. The complexity of fatty acid profile of this strain was revealed by GC and GC-MS. Treatment of cells with cerulenin resulted in significantly reduced level of C16 monounsaturated fatty acid (C16:1(Δ9t), C16:1(Δ7)). In contrast, the amount of saturated fatty acids (C10:0, C12:0, C14:0), hydroxyl fatty acids (3-OH C10:0 and 3-OH C12:0), as well as C20:4ω3, C20:5ω3 and C22:6ω3 were increased. RNA sequencing (RNA-Seq) revealed the altered gene expression pattern when C. psychrerythraea cells were treated with cerulenin. Genes involved in polyketide synthase pathway and fatty acid biosynthesis pathway were not obviously affected by cerulenin treatment. In contrast, several genes involved in fatty acid degradation or β-oxidation pathway were dramatically reduced at the transcriptional level. Genes responsible for DHA formation in C. psychrerythraea was first cloned and characterized. We revealed the complexity of fatty acid profile in this DHA-producing strain. Cerulenin could substantially change the fatty acid composition by affecting the fatty acid degradation at transcriptional level. Acyl-CoA dehydrogenase gene family involved in the first step of β-oxidation pathway may be important to the selectivity of degraded fatty acids. In addition, inhibition of FabB protein by cerulenin may lead to the accumulation of malonyl-CoA, which is the substrate for DHA formation.

Recommendations to the NRC for review criteria for alternative methods of low-level radioactive waste disposal: Task 2b: Earth-mounded concrete bunkers

International Nuclear Information System (INIS)

Denson, R.H.; Bennett, R.D.; Wamsley, R.M.; Bean, D.L.; Ainsworth, D.L.

1988-01-01

The US Army Engineers Waterways Experiment Station (WES) and US Army Engineer Division, Huntsville (HNDED) have developed general design criteria and specific design review criteria for the earth-mounded concrete bunker (EMCB) alternative method of low-level radioactive waste (LLW) disposal. An EMCB is generally described as a reinforced concrete vault placed below grade, underneath a tumulus, surrounded by filter-blanket and drainage zones. The tumulus is covered over with a low permeability cover layer and top soil with vegetation. Eight major review criteria categories have been developed ranging from the loads imposed on the EMCB structure through material quality and durability considerations. Specific design review criteria have been developed in detail for each of the eight major categories. 63 refs., 13 figs., 2 tabs

Is “Islamic Fundamentalism” Possible?

Directory of Open Access Journals (Sweden)

Neşet TOKU

2015-12-01

Full Text Available Fundamentalism is the religious Protestant movement that developed upon the spreading of the “millennium” belief, which belongs to the Christian theo-logy, in the USA towards the end of 19th century. Nowadays the word “funda-mentalism” is used, sometimes explicitly and sometimes implicitly, to refer to Islam as an equivalent of intolerance, pro-violence and fanaticism. This propa-ganda is so great that recognition of Islam by a Muslim raises the risk for him to be qualified as fundamentalist. In this essay, we will interrogate whether it is possible or not to establish a relation between fundamentalism, which is a wes-tern phenomenon, and Islam by examining historical and cultural background of the both.

Identification of two novel pathogenic compound heterozygous MYO7A mutations in Usher syndrome by whole exome sequencing.

Science.gov (United States)

Jia, Ying; Li, Xiaoge; Yang, Dong; Xu, Yi; Guo, Ying; Li, Xin

2018-01-01

The current study aims to identify the pathogenic sites in a core pedigree of Usher syndrome (USH). A core pedigree of USH was analyzed by whole exome sequencing (WES). Mutations were verified by polymerase chain reaction (PCR) amplification and Sanger sequencing. Two pathogenic variations (c.849+2T>C and c.5994G>A) in MYO7A were successfully identified and individually separated from parents. One variant (c.849+2T>C) was nonsense mutation, causing the protein terminated in advance, and the other one (c.5994G>A) located near the boundary of exon could cause aberrant splicing. This study provides a meaningful exploration for identification of clinical core genetic pedigrees. Copyright © 2017 Elsevier B.V. All rights reserved.

Fatalism and its implications for risky road use and receptiveness to safety messages: a qualitative investigation in Pakistan.

Science.gov (United States)

Kayani, A; King, M J; Fleiter, J J

2012-12-01

Given the increasing vehicle numbers and expanding road construction in developing countries, the importance of safe road user behaviour is critical. Road traffic crashes (RTCs) are a significant problem in Pakistan; however, the factors that contribute to RTCs in Pakistan are not well researched. Fatalistic beliefs are a potential barrier to the enhancement of road safety, especially participation in health-promoting and injury prevention behaviours, and also contribute to risk taking. Fatalistic beliefs relating to road safety have been found in some developing countries, although research is scarce and indicates that the nature and extent of fatalism differs in each country. Qualitative research was undertaken with a range of drivers, religious orators, police and policy makers to explore associations between fatalism, risky road use and associated issues. Findings indicate that fatalistic beliefs are pervasive in Pakistan, are strongly linked with religion, present a likely barrier to road safety messages and contribute to risky road use. Fatalism appears to be a default attribution of RTC and the intensity of belief in fate surpasses the kinds of fatalism noted in the limited existing literature. These findings have importance to developing road safety countermeasures in countries where fatalistic beliefs are strong.

Amorphous Dielectric Thin Films with Extremely Low Mechanical Loss

Directory of Open Access Journals (Sweden)

Liu X.

2015-04-01

Full Text Available The ubiquitous low-energy excitations are one of the universal phenomena of amorphous solids. These excitations dominate the acoustic, dielectric, and thermal properties of structurally disordered solids. One exception has been a type of hydrogenated amorphous silicon (a-Si:H with 1 at.% H. Using low temperature elastic and thermal measurements of electron-beam evap-orated amorphous silicon (a-Si, we show that TLS can be eliminated in this system as the films become denser and more structurally ordered under certain deposition conditions. Our results demonstrate that TLS are not intrinsic to the glassy state but instead reside in low density regions of the amorphous network. This work obviates the role hydrogen was previously thought to play in removing TLS in a-Si:H and favors an ideal four-fold covalently bonded amorphous structure as the cause for the disappearance of TLS. Our result supports the notion that a-Si can be made a “perfect glass” with “crystal-like” properties, thus offering an encouraging opportunity to use it as a simple crystal dielectric alternative in applications, such as in modern quantum devices where TLS are the source of dissipation, decoherence and 1/f noise.

In My Day: Using lessons from history, ritual and our elders to build professional identity.

Science.gov (United States)

McAllister, Margaret; John, Tracey; Gray, Michelle

2009-07-01

Drawing on the power of ritual, storytelling and lessons from history and our professional elders, nursing academics at the University of the Sunshine Coast organised a three-hour event on International Nurses Day. The aims were to model to students the importance of producing their own nursing stories and to celebrate and stimulate conversation about the diverse, rich, local and national history of nursing. The event included: an oration from an influential guest speaker; video footage of nurses telling their stories; an historical display of nursing artefacts; opportunities for participants to record their stories; and opportunities for students, staff and the local nursing fraternity to engage with each other. The event received very positive evaluative feedback from participants, and we formulated recommendations for future events and student education: (1) ensure an adequate planning period to book a suitable venue and elicit sufficient financial and marketing support; (2) establish a local retired nurses association that could provide mentoring support for student nurses; and (3) integrate the annual event and the mentoring program into the curriculum of a course within our Nursing Program. We conclude that such professional development events can provide many benefits for all sectors of our nursing community.

A poesia épica na construção dos Discursos de Dion Crisóstomo = Epic poetry in the construction of Dion Chrysostom’s Discourses

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Andrea Lucia Dorini de Oliveira Carvalho Rossi

2010-01-01

Full Text Available Ao elaborar os seus Discursos, Dion Crisóstomo se vale das referênciasconstantes de Homero para a construção de imagens. Ao usar as imagens presentes na poesia épica grega, Dion Crisóstomo evoca as representações imagéticas presentes na literatura para difundir suas ideias filosóficas e políticas durante o final do Século I d.C sobos governos de Domiciano, Nerva e Trajano. Ao se fazer a análise desse autor, pretende-se também discutir a literatura como uma das formas de representação da identidade helenística sob o Principado Romano.The construction of images in the speeches of Dion Chrysostom was drawn from references in Homer. When the orator uses images from Greek epic poetry, Dion Chrysostom intimates the representation of images found in the literature to propagate his philosophical and political ideas during the first century A.D. under the administration of the emperors Domitian, Nerva and Trajan. Current analysis of the author’s works discusses literature as one of the representational forms of Hellenistic identity under Romandomination.

PENDIDIKAN KARAKTER POLA MUHAMMADIYAH (Studi Kasus SMA Muhammadiyah 1 dan MA Muallimin Yogyakarta

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Kuswono Kuswono

2013-09-01

Full Text Available This research aims to find out the sources of character education at Islamic schools, character- building values application and actualization. This research was conducted in SMA Mubammadiyah I Yogyakarta and MA Muallimin Muhammadiyah Yogyakarta.The result of research showed that teacher's perception on character education relied on Islamic precepts to create akhakul karimah-human beings. The sources of character education included Quran and as=Sunnah/Hadist as well as Ijtihad. The character value implantation was carried out through learning in the classroom, precedents from figures, teachers and peers, well-behaving familiarization in the presence of rule and order, personality report, and extracurricular activities in knowledge, skill, sport, art, and organization fields. The form of character-building values actualization emphasized more on the Islamic activities such as collectively shalat, reading and reciting Quran, social service, participating actively in IPM, hizbul wathan, and tapak suci organizational activities. In addition, there were kader inti/an, mubalig jumat, mubalig hijarah, fasting, Friday sermon, becoming the orator in pengajian, and flag ceremony. Such these activities reflected on religious, cooperative, leadership, loving-to-homeland, social care, environmental care, and creative values.Keywords: Education, Character, Muhammadiyah.

"Peintre de Sa Majesté Britannique". Franz Adolph of Freenthal and his portrait of Maximilian Hamilton, Prince-Bishop of Olomouc

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Suchánek, Pavel

2012-09-01

Full Text Available This essay examines the portrait of Maximilian von Hamilton (1714-1776, the last Prince-Bishop of Olomouc/Olmütz, painted between 1769 and 1772 by Franz Adolph of Freenthal (1721-1773, a former painter to the British royal court. The study focuses in turn on three visual motifs in Hamilton's portrait: the rhetorical gestures of the sitter, his attire and the way he is depicted, and the form of presentation and the function of the painting in the ceremonial space of the princely residence. In examining each of these motifs, account is taken of the specific visual conventions applied in this genre, and of the contemporary rules of visual rhetoric. By referencing the classical motif of modesty and moderation from antiquity, Adolph underlined the importance of the ideal of antiquity and with it "natural" speech and behaviour. He attempted to express the spirit of antiquity by comparing contemporary clothing and rhetorical gestures to those of the orators or other public figures of antiquity. In a similar way to contemporary British painters, he thus referenced models taken from antiquity, with the aim of evoking a noble past and representing the ideal of the virtue of antiquity.

Oration ”Ut apertum vobis” of Pope Pius II (10 October 1458, Rome). Edited and translated by Michael v. Cotta-Schönberg. Preliminary edition, 2nd version. With the papal bull “Vocavit nos Pius”. (Orations of Enea Silvio Piccolomini / Pope Pius II; 29) :

OpenAIRE

Cotta-Schønberg, Michael

2015-01-01

Immediately after his election in August 1458, Pope Pius II began to plan for a crusade against the Turks, a cause he had worked for tirelessly since the Fall of Constantinople. He soon decided that the most effective way would be to summon the European kings and princes to a congress on the matter, to be held in a city in Northern Italy which would be more accessible for the participants from beyond the Alps than the City of Rome. After intense consultations with the cardinals, the pope form...

First applications of a targeted exome sequencing approach in fetuses with ultrasound abnormalities reveals an important fraction of cases with associated gene defects

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Constantinos Pangalos

2016-04-01

Full Text Available Background. Fetal malformations and other structural abnormalities are relatively frequent findings in the course of routine prenatal ultrasonographic examination. Due to their considerable genetic and clinical heterogeneity, the underlying genetic cause is often elusive and the resulting inability to provide a precise diagnosis precludes proper reproductive and fetal risk assessment. We report the development and first applications of an expanded exome sequencing-based test, coupled to a bioinformatics-driven prioritization algorithm, targeting gene disorders presenting with abnormal prenatal ultrasound findings. Methods. We applied the testing strategy to14 euploid fetuses, from 11 on-going pregnancies and three products of abortion, all with various abnormalities or malformations detected through prenatal ultrasound examination. Whole exome sequencing (WES was followed by variant prioritization, utilizing a custom analysis pipeline (Fetalis algorithm, targeting 758 genes associated with genetic disorders which may present with abnormal fetal ultrasound findings. Results. A definitive or highly-likely diagnosis was made in 6 of 14 cases (43%, of which 3 were abortuses (Ellis-van Creveld syndrome, Ehlers-Danlos syndrome and Nemaline myopathy 2 and 3 involved on-going pregnancies (Citrullinemia, Noonan syndrome, PROKR2-related Kallmann syndrome. In the remaining eight on-going pregnancy cases (57%, a ZIC1 variant of unknown clinical significance was detected in one case, while in seven cases testing did not reveal any pathogenic variant(s. Pregnancies were followed-up to birth, resulting in one neonate harboring the PROKR2 mutation, presenting with isolated minor structural cardiac abnormalities, and in seven apparently healthy neonates. Discussion. The expanded targeted exome sequencing-based approach described herein (Fetalis, provides strong evidence suggesting a definite and beneficial increase in our diagnostic capabilities in prenatal

Isolation and Characterization of Electrochemically Active Subsurface Delftia and Azonexus Species

Science.gov (United States)

Jangir, Yamini; French, Sarah; Momper, Lily M.; Moser, Duane P.; Amend, Jan P.; El-Naggar, Mohamed Y.

2016-01-01

Continental subsurface environments can present significant energetic challenges to the resident microorganisms. While these environments are geologically diverse, potentially allowing energy harvesting by microorganisms that catalyze redox reactions, many of the abundant electron donors and acceptors are insoluble and therefore not directly bioavailable. Extracellular electron transfer (EET) is a metabolic strategy that microorganisms can deploy to meet the challenges of interacting with redox-active surfaces. Though mechanistically characterized in a few metal-reducing bacteria, the role, extent, and diversity of EET in subsurface ecosystems remains unclear. Since this process can be mimicked on electrode surfaces, it opens the door to electrochemical techniques to enrich for and quantify the activities of environmental microorganisms in situ. Here, we report the electrochemical enrichment of microorganisms from a deep fractured-rock aquifer in Death Valley, CA, USA. In experiments performed in mesocosms containing a synthetic medium based on aquifer chemistry, four working electrodes (WEs) were poised at different redox potentials (272, 373, 472, 572 mV vs. SHE) to serve as electron acceptors, resulting in anodic currents coupled to the oxidation of acetate during enrichment. The anodes were dominated by Betaproteobacteria from the families Comamonadaceae and Rhodocyclaceae. A representative of each dominant family was subsequently isolated from electrode-associated biomass. The EET abilities of the isolated Delftia strain (designated WE1-13) and Azonexus strain (designated WE2-4) were confirmed in electrochemical reactors using WEs poised at 522 mV vs. SHE. The rise in anodic current upon inoculation was correlated with a modest increase in total protein content. Both genera have been previously observed in mixed communities of microbial fuel cell enrichments, but this is the first direct measurement of their electrochemical activity. While alternate

A Novel Missense Mutation in SLC5A5 Gene in a Sudanese Family with Congenital Hypothyroidism.

Science.gov (United States)

Watanabe, Yui; Ebrhim, Reham Shareef; Abdullah, Mohamed A; Weiss, Roy E

2018-05-15

Thyroid hormone synthesis requires the presence of iodide. The sodium iodide symporter (NIS) is a glycoprotein which mediates the active uptake of iodide from the blood stream into the thyroid grand. NIS defects due to SLC5A5 gene mutations are known to cause congenital hypothyroidism (CH). The proposita is a 28-year-old female whose origin is the North Sudan where neonatal screening for CH is not available. She presented with severe constipation and a goiter at the age of 40 days. Laboratory testing confirmed CH and she was started on levothyroxine (L-T4). Presumably due to the delayed treatment the patient developed mental retardation. Her younger sister presented with a goiter, tongue protrusion and umbilical hernia and the youngest brother was also diagnosed with CH based on the TSH >100 µIU/mL at the age of 22 days and 8 days, respectively. Two siblings were treated with L-T4 and had normal development. Their consanguineous parents had no history of thyroid disorders. We performed whole exome sequencing (WES) on the proposita. WES identified a novel homozygous missense mutation in the SLC5A5 gene: c.1042T>G, p.Tyr348Asp, which was subsequently confirmed by Sanger sequencing. All affected children were homozygous for the same mutation and their unaffected mother was heterozygous. The NIS protein is composed of 13 transmembrane segments (TMS), an extracellular amino-terminus and an intracellular carboxyl terminus. The mutation is located in the TMS IX which has the most β-OH group-containing amino acids (serine and threonine) which is implicated in Na+ binding and translocation. In conclusion, a novel homozygous missense mutation in the SLC5A5 gene was identified in the Sudanese family with CH. The mutation is located in the TMS IX of the NIS protein which is essential for NIS function. Low iodine intake in Sudan is considered to affect severity of hypothyroidism in the patients.

Childhood leukodystrophies: A literature review of updates on new definitions, classification, diagnostic approach and management.

Science.gov (United States)

Ashrafi, Mahmoud Reza; Tavasoli, Ali Reza

2017-05-01

Childhood leukodystrophies are a growing category of neurological disorders in pediatric neurology practice. With the help of new advanced genetic studies such as whole exome sequencing (WES) and whole genome sequencing (WGS), the list of childhood heritable white matter disorders has been increased to more than one hundred disorders. During the last three decades, the basic concepts and definitions, classification, diagnostic approach and medical management of these disorders much have changed. Pattern recognition based on brain magnetic resonance imaging (MRI), has played an important role in this process. We reviewed the last Global Leukodystrophy Initiative (GLIA) expert opinions in definition, new classification, diagnostic approach and medical management including emerging treatments for pediatric leukodystrophies. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Recommendations to the NRC for review criteria for alternative methods of low-level radioactive waste disposal: Task 2a, Below-ground vaults

International Nuclear Information System (INIS)

Denson, R.H.; Bennett, R.D.; Wamsley, R.M.; Bean, D.L.; Ainsworth, D.L.

1987-12-01

The US Army Engineer Waterways Experiment Station (WES) and the US Army Engineer Division, Huntsville (HNDED) have developed general design criteria and specific design review criteria for the below-ground vault (BGV) alternative method of low-level radioactive waste (LLW) disposal. A BGV is a reinforced concrete vault (floor, walls, and roof) placed underground below the frost line, and above the water table, surrounded by filter blanket and drainage zones and covered with a low permeability earth layer and top soil with vegetation. Eight major review criteria categories have been developed ranging from the loads imposed on the BGV structure through material quality and durability considerations. Specific design review criteria have been developed in detail for seven of the eight major categories. 59 refs., 14 figs., 2 tabs

Computer Program Development Specification Terminal-to-Host Protocol (THP). Revision 2.

Science.gov (United States)

1980-02-08

Pitauesting the new e@"owctlam, offectiveIvo ockma1eacil. t @q 0’@e!40P. I# a "-G!e"o~ 00*04 POzWes2 is "at pece ~fees witm4m a*a teim time #p4-, !"e...Status emmeado TNP will ghOld Of#5 ueep*?o twoPk lot* dwueo Otio IOn Ooet4 at Oe A peoauI 4F* en oseo of CCJ/TAC #Iow coAtpol oe 04isms, ovIsio" 20...3oS.ver Vept4Ca1 Too (VT) CmaraCto.. V.I1jq of VT to Me pece ~vOO 0, Wep PSEC Sev~ Epase ca.acto CEc) c’apaetep. Valu a#EC to to po*@4v*o Ov wop~. PSEL

Further contribution to the diatom flora of sewage enriched waters in southern Africa

CSIR Research Space (South Africa)

Schoeman, FR

1972-01-01

Full Text Available PHYCOLOGI A 11(3/4 ) 1972 . A furthe r contributio n t o th e diato m flor a o f sewag e enriche d water s i n souther n Afric a F . R . ScH0EMA N Counci l fo r Scientifi c an d industria l Research , Nationa l institut e fo r Wate r Research , Pretoria... , Republi c o f Sout h Afric a Accepte d Jun e 12 , 197 2 Th e systematic s an d autecolog y o f th e diatom s observe d i n a n alga l sampl e fro m a maturatio n pon d o f th e Walvi s Ba y (Sout h Wes t Africa n coast ) sewag e work s ar e discussed...

Political Events through Image and Ritual

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Mirela Arsith

2013-07-01

Full Text Available Governing people, the manifestation of the political power event creates beliefs and ideas - power which represent variables of belief systems or existing rules in any society. Some promote emancipation, freedom and justice, others propagate retaliation, revenge and oppression. All, however, serve the approaches to mobilize and unite people through images and speech. The image is a global view of the person. It comes from personal experience and from the information received from the media and is the synthesis of all we know, true or false, on the subject which it represents. The citizens perceive the politician, the party, the political organization or institution according to the promoted image. The unique form of political discourse in the minds of the audience induces in the mind of the auditory the faith in the ability of the orator to provide optimal solutions to the problems manifested in the society. The charismatic leader acquires much of his power from the fact that it is perceived by many as being simultaneously above others and as others. The charismatic leader knows that energy of the masses is extracted from the emotions, illusions, beliefs, expectations, ideals and dreams; thus energized, people believe they know who to follow and who to devote.

One night of sleep loss impairs innovative thinking and flexible decision making.

Science.gov (United States)

Harrison, Y; Horne, J A

1999-05-01

Recent findings with clinically oriented neuropsychological tests suggest that one night without sleep causes particular impairment to tasks requiring flexible thinking and the updating of plans in the light of new information. This relatively little investigated field of sleep deprivation research has real-world implications for decision makers having lost a night's sleep. To explore this latter perspective further, we adapted a dynamic and realistic marketing decision making "game" embodying the need for these skills, and whereby such performance could be measured. As the task relied on the comprehension of a large amount of written information, a critical reasoning test was also administered to ascertain whether any failure at the marketing game might lie with information acquisition rather than with failures in decision making. Ten healthy highly motivated and trained participants underwent two counterbalanced 36 h trials, sleep vs no sleep. The critical reasoning task was unaffected by sleep loss, whereas performance at the game significantly deteri orated after 32-36 h of sleep loss, when sleep deprivation led to more rigid thinking, increased perseverative errors, and marked difficulty in appreciating an updated situation. At this point, and despite the sleep-deprived participants' best efforts to do well, their play collapsed, unlike that of the nonsleep-deprived participants. Copyright 1999 Academic Press.

Measurement of heavy quark forward-backward asymmetries and the B mixing parameter using Z decays recorded with the OPAL detector at LEP

CERN Document Server

Krämer, Thomas; Büßer, F W

2004-01-01

This thesis deals with the measuremen t of the b and c quark forw ard-bac kward asymmetries of hadronic Z deca ys recorded with the OP AL exp erimen t at the electron positron collider LEP . After an overview over the di eren t kinds of hea vy avour forw ard-bac kward asymmetry measuremen ts made within the OP AL col- lab oration, one of the metho ds is describ ed in full detail. This metho d is based on the semileptonic b and c quark deca ys in order to identify primary b b and c c events. Tw o neural net works are used to separate the b b and c c events from eac h other and from the bac kground. The rst neural net work is trained to identify b->l-, the second to iden tify c ! ` + deca ys. A maxim um likeliho od t is used to extract the b and c quark forw ard-bac kward asymmetries A b FB and A c FB at three cen tre-of-mass energies p s and the average B mixing parameter from a sample with at least one iden ti ed electron or muon in the nal state. (not complete)

Imaging analysis of heart movement for improving the respiration-gated radiotherapy in patients with left sided breast cancer

Energy Technology Data Exchange (ETDEWEB)

Abdelhamid, Rania; Farrag, A.; Khalifa, A. [Clinical Oncology Department, Assiut University (Egypt); Block, Andreas [Institut fuer Medizinische Strahlenphysik und Strahlenschutz, Klinikum Dortmund (Germany)

2012-07-01

Respiration induced heart movement during radiotherapy exposes the heart to the inevitable risks of radio-exposure, and hence radiation injury, in cases of Lt. sided breast cancer. The impact of such a risk is additionally aggravated by the use of radiotherapy in combination with cardiotoxic chemotherapeutic agents. Radio-oncologists pay special attention to the coronary arteries that might be included in this small part of the heart exposed to radiation. The aim of this study was to include the internal heart movement for improving respiration-gated radiotherapy of left sided breast cancer. For 70 patients, all females left sided breast cancer, two planning CT's in inspiration and expiration, and one free breathing scan are performed. The heart motion was analyzed with the clinic-developed software ORAT in the simulator sequence for acquiring information of the cranio-caudal amplitude of heart movements in free breathing (respiration-induced amplitude) and a 15 seconds breath-hold phase (inherent amplitude). The role of inherent heart movement varies from one patient to another which should be taken in consideration during defining the parameters of respiration-gated radiotherapy. The inherent amplitude of the heart motion is the physiological lower limit of the respiration-gating window.

Case Report: Whole exome sequencing reveals a novel frameshift deletion mutation p.G2254fs in COL7A1 associated with autosomal recessive dystrophic epidermolysis bullosa [version 2; referees: 2 approved, 1 approved with reservations

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Shamsudheen Karuthedath Vellarikkal

2016-07-01

Full Text Available Dystrophic epidermolysis bullosa simplex (DEB is a phenotypically diverse inherited skin fragility disorder. It is majorly manifested by appearance of epidermal bullae upon friction caused either by physical or environmental trauma. The phenotypic manifestations also include appearance of milia, scarring all over the body and nail dystrophy. DEB can be inherited in a recessive or dominant form and the recessive form of DEB (RDEB is more severe. In the present study, we identify a novel p.G2254fs mutation in COL7A1 gene causing a sporadic case of RDEB by whole exome sequencing (WES. Apart from adding a novel frameshift Collagen VII mutation to the repertoire of known mutations reported in the disease, to the best of our knowledge, this is the first report of a genetically characterized case of DEB from India.

Case Report: Whole exome sequencing reveals a novel frameshift deletion mutation p.G2254fs in COL7A1 associated with autosomal recessive dystrophic epidermolysis bullosa [version 1; referees: 2 approved, 1 approved with reservations

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Shamsudheen Karuthedath Vellarikkal

2016-05-01

Full Text Available Dystrophic epidermolysis bullosa simplex (DEB is a phenotypically diverse inherited skin fragility disorder. It is majorly manifested by appearance of epidermal bullae upon friction caused either by physical or environmental trauma. The phenotypic manifestations also include appearance of milia, scarring all over the body and nail dystrophy. DEB can be inherited in a recessive or dominant form and the recessive form of DEB (RDEB is more severe. In the present study, we identify a novel p.G2254fs mutation in COL7A1 gene causing a sporadic case of RDEB by whole exome sequencing (WES. Apart from adding a novel frameshift Collagen VII mutation to the repertoire of known mutations reported in the disease, to the best of our knowledge, this is the first report of a genetically characterized case of DEB from India.

Nuclear Criticality Safety Department Qualification Program

International Nuclear Information System (INIS)

Carroll, K.J.; Taylor, R.G.; Worley, C.A.

1996-01-01

The Nuclear Criticality Safety Department (NCSD) is committed to developing and maintaining a staff of highly qualified personnel to meet the current and anticipated needs in Nuclear Criticality Safety (NCS) at the Oak Ridge Y-12 Plant. This document defines the Qualification Program to address the NCSD technical and managerial qualification as required by the Y-1 2 Training Implementation Matrix (TIM). This Qualification Program is in compliance with DOE Order 5480.20A and applicable Lockheed Martin Energy Systems, Inc. (LMES) and Y-1 2 Plant procedures. It is implemented through a combination of WES plant-wide training courses and professional nuclear criticality safety training provided within the department. This document supersedes Y/DD-694, Revision 2, 2/27/96, Qualification Program, Nuclear Criticality Safety Department There are no backfit requirements associated with revisions to this document

Produtividade e exportação de nutrientes em beterraba cultivada com cobertura morta e adubação orgânica Yield and nutrient export of sugar beet under mulching and organic fertilization

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Maria A. N. Sediyama

2011-09-01

Full Text Available Objetivou-se, com este trabalho, avaliar o efeito da cobertura do solo e doses de lodo de lagoa de decantação de água residuária de suinocultura na produtividade e na exportação de nutrientes pela beterraba, cultivar Early Wonder. O experimento foi conduzido na Fazenda Experimental Vale do Piranga, pertencente à EPAMIG, Zona da Mata, em Oratórios, MG, no período de 07/08/08 a 09/11/08, no delineamento de blocos casualizados em parcelas subdivididas com quatro repetições. Nas parcelas foram dispostos três tipos de cobertura de solo: bagaço de cana-de-açúcar, palha de café e sem cobertura e, nas subparcelas, foram usadas cinco doses do lodo de lagoa: 0; 10; 20; 40 e 60 t ha-1. Aos 70 dias após o transplante das mudas realizou-se a colheita. A cobertura com palha de café proporcionou maior massa unitária de raiz e maior produtividade de raízes comerciais, independente das doses de lodo. Os nutrientes mais exportados pela parte aérea das plantas foram Ca, Mg e S e, pelas raízes, N, P e K. Com a população de 400.000 plantas ha-1e produtividade de 34,22 t ha-1, as quantidades médias de N, P, K, Ca, Mg e S exportadas pelas raízes foram 140; 24; 180; 8, 17 e 5 kg ha-1e, para Zn, Fe, Mn, Cu e B, 371, 435, 320, 74 e 250 g ha-1, respectivamente.This work aimed to evaluate the effect of soil cover and doses of sludge from sedimentation pond of swine wastewater on yield and nutrient export in sugar beet cultivar Early Wonder. The experiment was conducted at the Vale do Piranga Experimental Farm belonging to EPAMIG Zona da Mata in Oratórios (MG, from 07/08/08 to 09/11/08. The experiment was arranged in a split-plot in randomized block design with four replications. The main plots consisted of three types of mulching: sugarcane bagasse, coffee husk and without any cover, and the subplots of five doses of sludge: 0, 10, 20, 40 and 60 t ha-1. At 70 days after transplanting, harvest was carried out. Mulching with coffee husk provided

Avaliação de herbicidas no controle de plantas daninhas em mandioquinha-salsa Herbicide efficiency in controlling weeds in peruvian carrot

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Maria Aparecida Nogueira Sediyama

2008-12-01

Full Text Available Avaliou-se a eficiência de herbicidas aplicados em pré e pós-emergência no controle de plantas daninhas e na produção de mandioquinha-salsa na Fazenda Experimental da EPAMIG, em Oratórios (MG, de maio a dezembro de 2002. Utilizou-se o delineamento de blocos casualizados com quatro repetições e 15 tratamentos incluindo duas testemunhas, com e sem capina. Em cada tratamento, foi usado um herbicida em pré e outro em pós-emergência das plantas, aplicados aos três e aos 45 dias após o plantio (DAP respectivamente. A eficiência de controle e a toxidez dos herbicidas foram avaliadas aos 60 DAP e a produção de matéria seca de plantas daninhas aos 60 e 130 DAP. Na colheita, avaliou-se produção de raízes, coroa e parte aérea. A emergência de plantas foi máxima aos 45 DAP e, posteriormente, houve redução no estande, quando se utilizaram os herbicidas atrazine + óleo mineral e oxadiazon, em pós-emergência. Esses herbicidas, apesar de eficientes no controle de plantas daninhas, causaram toxidez à cultura. Na produção de raízes, destacaram-se os tratamentos: atrazine +fluazifop-p-butil; diuron + fluazifop-p-butil; diuron + Oxadiazon; linuron + fluazifop-p-butil; metolachlor + metribuzin + linuron e oxadiazon + diuron, com bom controle de plantas daninhas e rendimentos de raízes comerciais semelhantes ao da testemunha mantida no limpo (8,62 t ha-1.The efficiency of herbicides applied in pre- and post-emergence for weed control in Peruvian carrot production was evaluated at the EPAMIG Experimental Farm, Oratórios, Minas Gerais State, from May to December, 2002. The experiment was arranged in a randomized block design, with four replications and 15 treatments, including two controls (with and without weeding. Pre- and post-emergence herbicides were used in each treatment applied at 3 and 45 days after planting (DAP, respectively. Efficiency and toxicity were evaluated at 60 DAP and weed dry matter yield at 60 and 130 DAP. At

Divinacija prieš Cecilijų Cicerono retorikos kontekste. Divinatio in Caecilium in the context of Cicero’s rhetoric

Directory of Open Access Journals (Sweden)

Audronė Kučinskienė

2010-01-01

Full Text Available In the well known episode in the Divination against Caecilius (Divinatio in Caecilium 27–46, Cicero, assuming the role of a teacher, expounds issues of rhetoric to his opponent. In this article the following points are examined: 1 the relation of this episode to the theory of rhetoric of the time, as represented in the unknown author’s Rhetorica ad Herennium and Cicero’s De inventione, which he wrote as a young man; 2 the repercussions of this episode in Cicero’s later works of rhetoric; 3 the relation of this episode to the other speeches against Verres.In Div. Caec. 27–46, Cicero does not try to set forth his material systematically and sequentially, as it is customary in rhetorical treatises, but directs his attention first at the moral qualities of a good orator, as well as on his education and the innate personal traits that form a perfect orator. This allows us to connect the Divination against Caecilius with Cicero’s later treatises on rhetoric, in particular De oratore. Being a supporter of philosophical rhetoric, Cicero disdains the traditional Hellenistic manuals that expound rhetorical technique. He does not try to teach these things – which would be the aim of a rhetoric manual – but he presumes that his audience would understand them from the small hints about the topics that must be recognised as coming from the school of rhetoric. Such a stance corresponds well to the spirit of the treatise De oratore: in that work, Cicero does not teach rules and does not explain rhetorical technique either, but, having mastered these things perfectly himself, he addresses his work to those readers who know the art of rhetoric and who would certainly recognise and appreciate the hints on the art of rhetoric, which are scattered through the text rather than explicitly demonstrated.In the episode Div. Caec. 27–46, Cicero uses va­rious rhetorical figures copiously and inventively. It is obvious that, in explaining the issues of

Survival of Salmonella enterica in poultry feed is strain dependent.

Science.gov (United States)

Andino, Ana; Pendleton, Sean; Zhang, Nan; Chen, Wei; Critzer, Faith; Hanning, Irene

2014-02-01

Feed components have low water activity, making bacterial survival difficult. The mechanisms of Salmonella survival in feed and subsequent colonization of poultry are unknown. The purpose of this research was to compare the ability of Salmonella serovars and strains to survive in broiler feed and to evaluate molecular mechanisms associated with survival and colonization by measuring the expression of genes associated with colonization (hilA, invA) and survival via fatty acid synthesis (cfa, fabA, fabB, fabD). Feed was inoculated with 1 of 15 strains of Salmonella enterica consisting of 11 serovars (Typhimurium, Enteriditis, Kentucky, Seftenburg, Heidelberg, Mbandanka, Newport, Bairely, Javiana, Montevideo, and Infantis). To inoculate feed, cultures were suspended in PBS and survival was evaluated by plating samples onto XLT4 agar plates at specific time points (0 h, 4 h, 8 h, 24 h, 4 d, and 7 d). To evaluate gene expression, RNA was extracted from the samples at the specific time points (0, 4, 8, and 24 h) and gene expression measured with real-time PCR. The largest reduction in Salmonella occurred at the first and third sampling time points (4 h and 4 d) with the average reductions being 1.9 and 1.6 log cfu per g, respectively. For the remaining time points (8 h, 24 h, and 7 d), the average reduction was less than 1 log cfu per g (0.6, 0.4, and 0.6, respectively). Most strains upregulated cfa (cyclopropane fatty acid synthesis) within 8 h, which would modify the fluidity of the cell wall to aid in survival. There was a weak negative correlation between survival and virulence gene expression indicating downregulation to focus energy on other gene expression efforts such as survival-related genes. These data indicate the ability of strains to survive over time in poultry feed was strain dependent and that upregulation of cyclopropane fatty acid synthesis and downregulation of virulence genes were associated with a response to desiccation stress.

International partnerships : a road map to success

International Nuclear Information System (INIS)

Hall, B.

2006-01-01

Green Breeze was founded in 2003, and was initially a small wind farm development company with 5 employees before creating partnerships with both local and North American companies in order to expand. The company now has 50 employees that work within 3 separate divisions, namely Green Breeze Energy Systems (GBES); Green Breeze Wind Park Development (GBWPD); and Compsotech. This presentation described the company's business strategy. GBES was created to meet market demand for small wind turbines. Barriers to success included the fact that market demand outweighed Canadian supply, and that Canadian suppliers were still challenged by technical issues. In order to maintain Canadian content and meet the needs of their clients, GBES formed a partnership with the Danish company WES to bring 80 kW and 250 kW turbines into Ontario. By partnering with WES, the company has been able to create a stable supply chain for customers while maintaining ties to Canadian turbine suppliers. GBWPD was created to develop utility-scale wind generation. The company did not win a contract in any recent requests for proposals (RFPs), which led them to conclude that smaller developers seemed to be excluded from the electricity market. As the aim of the organization was to develop projects and not simply model them, they have chosen to focus on smaller wind projects outside the RFP process. However, smaller projects have had limited access to financing and turbine suppliers. In order to address these issues GBWPD formed a partnership with ENERCON which provided financial support as well as access to German foundation specialists and the E48 turbine. Seven of the turbines are now planned for installation in 2007. The partnership has allowed GBWPD to bring over 150 MW of projects into their portfolio. In early 2006, Green Breeze bought controlling interest in Composotech Structures, a company specializing in structural composites manufacturing as well as turbine blade manufacturing and repair

Quantifying multi-dimensional functional trait spaces of trees: empirical versus theoretical approaches

Science.gov (United States)

Ogle, K.; Fell, M.; Barber, J. J.

2016-12-01

Empirical, field studies of plant functional traits have revealed important trade-offs among pairs or triplets of traits, such as the leaf (LES) and wood (WES) economics spectra. Trade-offs include correlations between leaf longevity (LL) vs specific leaf area (SLA), LL vs mass-specific leaf respiration rate (RmL), SLA vs RmL, and resistance to breakage vs wood density. Ordination analyses (e.g., PCA) show groupings of traits that tend to align with different life-history strategies or taxonomic groups. It is unclear, however, what underlies such trade-offs and emergent spectra. Do they arise from inherent physiological constraints on growth, or are they more reflective of environmental filtering? The relative importance of these mechanisms has implications for predicting biogeochemical cycling, which is influenced by trait distributions of the plant community. We address this question using an individual-based model of tree growth (ACGCA) to quantify the theoretical trait space of trees that emerges from physiological constraints. ACGCA's inputs include 32 physiological, anatomical, and allometric traits, many of which are related to the LES and WES. We fit ACGCA to 1.6 million USFS FIA observations of tree diameters and heights to obtain vectors of trait values that produce realistic growth, and we explored the structure of this trait space. No notable correlations emerged among the 496 trait pairs, but stepwise regressions revealed complicated multi-variate structure: e.g., relationships between pairs of traits (e.g., RmL and SLA) are governed by other traits (e.g., LL, radiation-use efficiency [RUE]). We also simulated growth under various canopy gap scenarios that impose varying degrees of environmental filtering to explore the multi-dimensional trait space (hypervolume) of trees that died vs survived. The centroid and volume of the hypervolumes differed among dead and live trees, especially under gap conditions leading to low mortality. Traits most predictive

Novel and rare functional genomic variants in multiple autoimmune syndrome and Sjögren's syndrome.

Science.gov (United States)

Johar, Angad S; Mastronardi, Claudio; Rojas-Villarraga, Adriana; Patel, Hardip R; Chuah, Aaron; Peng, Kaiman; Higgins, Angela; Milburn, Peter; Palmer, Stephanie; Silva-Lara, Maria Fernanda; Velez, Jorge I; Andrews, Dan; Field, Matthew; Huttley, Gavin; Goodnow, Chris; Anaya, Juan-Manuel; Arcos-Burgos, Mauricio

2015-06-02

Multiple autoimmune syndrome (MAS), an extreme phenotype of autoimmune disorders, is a very well suited trait to tackle genomic variants of these conditions. Whole exome sequencing (WES) is a widely used strategy for detection of protein coding and splicing variants associated with inherited diseases. The DNA of eight patients affected by MAS [all of whom presenting with Sjögren's syndrome (SS)], four patients affected by SS alone and 38 unaffected individuals, were subject to WES. Filters to identify novel and rare functional (pathogenic-deleterious) homozygous and/or compound heterozygous variants in these patients and controls were applied. Bioinformatics tools such as the Human gene connectome as well as pathway and network analysis were applied to test overrepresentation of genes harbouring these variants in critical pathways and networks involved in autoimmunity. Eleven novel and rare functional variants were identified in cases but not in controls, harboured in: MACF1, KIAA0754, DUSP12, ICA1, CELA1, LRP1/STAT6, GRIN3B, ANKLE1, TMEM161A, and FKRP. These were subsequently subject to network analysis and their functional relatedness to genes already associated with autoimmunity was evaluated. Notably, the LRP1/STAT6 novel mutation was homozygous in one MAS affected patient and heterozygous in another. LRP1/STAT6 disclosed the strongest plausibility for autoimmunity. LRP1/STAT6 are involved in extracellular and intracellular anti-inflammatory pathways that play key roles in maintaining the homeostasis of the immune system. Further; networks, pathways, and interaction analyses showed that LRP1 is functionally related to the HLA-B and IL10 genes and it has a substantial impact within immunological pathways and/or reaction to bacterial and other foreign proteins (phagocytosis, regulation of phospholipase A2 activity, negative regulation of apoptosis and response to lipopolysaccharides). Further, ICA1 and STAT6 were also closely related to AIRE and IRF5, two very

An exploration of relational aggression in the nursing workplace.

Science.gov (United States)

Dellasega, Cheryl; Volpe, Rebecca L; Edmonson, Cole; Hopkins, Margaret

2014-04-01

This study provides a 1st look at relational aggression (RA) and the consequences among nurses. Interpersonal hostility, bullying, and a toxic work environment (WE) can impact patient care delivery as well as nurses' personal health and job satisfaction. The Relational Aggression Assessment Scale, measuring aggressors, victims, and bystanders, was used to measure RA in a sample of 842 nurses. Additional variables measured included a demographic profile, job satisfaction, and intent to leave. Nurses were most likely to identify with victim behaviors, but a minority of nurses reported relying on aggressor behaviors and bystander behaviors. There was a positive correlation among aggressor, victim, and bystander items, suggesting overlap in roles. A few relationally aggressive individuals can create a toxic WE. Interventions to address RA among nurses must be tested, as well as strategies for improving job satisfaction and promoting healthy WEs through positive relationships.

Archived neonatal dried blood spot samples can be used for accurate whole genome and exome-targeted next-generation sequencing

DEFF Research Database (Denmark)

Hollegaard, Mads Vilhelm; Grauholm, Jonas; Nielsen, Ronni

2013-01-01

Dried blood spot samples (DBSS) have been collected and stored for decades as part of newborn screening programmes worldwide. Representing almost an entire population under a certain age and collected with virtually no bias, the Newborn Screening Biobanks are of immense value in medical studies......, for example, to examine the genetics of various disorders. We have previously demonstrated that DNA extracted from a fraction (2×3.2mm discs) of an archived DBSS can be whole genome amplified (wgaDNA) and used for accurate array genotyping. However, until now, it has been uncertain whether wgaDNA from DBSS...... can be used for accurate whole genome sequencing (WGS) and exome sequencing (WES). This study examined two individuals represented by three different types of samples each: whole-blood (reference samples), 3-year-old DBSS spotted with reference material (refDBSS), and 27- to 29-year-old archived...

Die meting van die invloed van organisasiegrootte op bruin werkers se houdings en gedrag

Directory of Open Access Journals (Sweden)

R. van der Bank

1985-11-01

'n Oorsig van die literatuur dui daarop dat bevindinge onkonsekwent is wat betref die invloed van die grootte van organisasies op veranderlikes soos die doeltreffendheid van personeel-keuringstelsels, opleiding, arbeidsomset, werkafwesigheid, werkdoeltreffendheid en so meer. In Wes-Kaapland is tien "groot" fabrieke geselekteer (aantal bruin werkers 300 of meer en vergelyk met 17 "klein" fabrieke (aantal bruin werkers minder as 50. Met behulp van t-toetse is statisties beduidende verskille gevind ten opsigte van die volgende veranderlikes waarvolgens groot organisasies meer gunstig vertoon: 1 meer keuringstegnieke word gebruik; 2 die doeltreffendheid van die keurings-programme is hoër; 3 meer opleidingstegnieke word gebruik; 4 opleidingsprogramme is meer doeltreffend; 5 werkers is meer tevrede; 6 werkers se gemiddelde beroepsaanpassing is beter, en 7 werkers is meer tevrede met hul salarisse of lone. Geen betekenisvolle verskille is egter gevind ten opsigte van arbeidsomset, werkafwesigheid en werkbehoeftes nie.

[Andreas Vesalius: his rich imagination and colorful detail account in his book: 'Research of the anatomical observations of Gabriel Falloppius'].

Science.gov (United States)

Gilias, Guy

2015-03-01

In a long letter, Andreas Vesalius reacts to the comments made by Gabriel Falloppius to his work 'De Humani Corporis Fabrica'. In this letter, he proves Falloppius wrong in a number of assertions and corrects him on more than one occasion. In doing so, Vesalius as a renaissance humanist uses a classic Latin language with long elegant sentences in the style of the old Roman orator Cicero. Remarkably interesting is the fact that this whole argumentation is spiced with comparisons and examples from daily life. To make it clear to the reader what a certain part of the skeleton looks like, he compares this part with an object everybody knows. All parts of the human body are depicted in such an almost graphic way that even an interested reader without any medical or anatomic education can picture them. And Vesalius is very creative in doing so, an artist as it were with a very rich imagination. Moreover, it's remarkable how the famous anatomist manages to put himself on the level of any ordinary person, using comparative images on that level. This last work of Vesalius, which he himself considers to be a supplement to his De Humani Corporis Fabrica, deserves special attention, not only because it illustrates the scientific evolution of the anatomist Vesalius, but also because it offers an insight in the psychology of that fascinating scientist Andreas Vesalius.

Homilia e educação cristã na Antiguidade Tardia: a relação corpo, igreja e cidade segundo João Crisóstomo - doi: 10.4025/actascieduc.v36i1.21972

Directory of Open Access Journals (Sweden)

Gilvan Ventura da Silva

2014-02-01

Full Text Available Um dos principais instrumentos empregados pela elite eclesiástica para obter a conversão de massa das populações urbanas nos séculos IV e V foram as homilias, gênero literário híbrido cujos primórdios remontam ao século II, mas que somente na Antiguidade Tardia adquire um papel de primeira grandeza quando se trata de realizar a transmissão rotineira dos ensinamentos evangélicos a uma audiência cada vez mais numerosa. Sem contar com escolas que pudessem estabilizar, no interior das congregações, um número crescente de egressos do paganismo e do judaísmo, as autoridades cristãs desenvolverão uma estratégia proselitista calcada no manejo excelente da arte oratória pelos pregadores. Tendo em vista essas considerações, pretendemos discutir em que medida as homilias contribuíram para a formação espiritual dos cristãos, enfatizando as normas visando a disciplinar o uso do corpo pelos fiéis na igreja, numa franca oposição às modalidades de exibição corporal na polis. Para tanto, investigamos o problema tendo como referência Antioquia e a atividade pastoral de João Crisóstomo nas últimas décadas do século IV.

The Political Commitment Poetry in the Poem of Abdullah Ebin Qaise Al Ruqayyiat. قصيدة الولاء السياسي في مديح عبد الله بن قيس الرقيات

Directory of Open Access Journals (Sweden)

Insaf Salman Alwan Aldalimi أنصاف سلمان علوان الدليمي

2017-09-01

Full Text Available The Thesis of our research is founded on the fact that a poen extoling the Governor praising ,which embraced the Umayyad Islamic rules in order to authorize them mentally to be accepted by society , and the caliphs were directing poets of praise to follow a specific line that is in accordance with specific standards, and not later than the poets responding to such desire as long as they get them in return for donations to the prices measured whether the laudatory term link to the praised caliphs everything religious and sacred . the Umayyad caliphs were retaining their real feelings of threat from peoples who compete on the caliphate and who viewed them as rapists, and so many claimants to the caliphate and multiple currents and political and parties , these parties have adopted in turn try to prove their theory in Islamic poetry . it wes a real loyalty to the caliph is that the mission to the praised caliphate was assingned divinely.

Cine-Club

CERN Document Server

Ciné-Club

2012-01-01

Projection from DVD – entrance 2 CHF for info http://cern.ch/Cineclub/ Thursday 12 July 2012 at 20:00 CERN Council Chamber The Darjeeling Limited By Wes Anderson (USA, 2007) With: Owen Wilson, Adrien Brody and Jason Schwartzmann Original version English; French subtitles; 91 minutes A year after the accidental death of their father, three drug-addicted brothers – each suffering from depression – meet for a train trip across India. Francis, the eldest, has organized it. The brothers argue, sulk, resent each other, and fight. The youngest, Jack, estranged from his girlfriend, is attracted to one of the train's attendants. Peter has left his pregnant wife at home, and he buys a venomous snake. After a few days, Francis discloses their surprising and disconcerting destination. Amid foreign surroundings, can the brothers sort out their differences? A funeral, a meditation, a hilltop ritual, and the Bengal Lancer figure in the reconciliation. * * * * * Thursday 19 J...

Vertical-axial component wind turbine with a high coefficient using for wind energy

International Nuclear Information System (INIS)

Yersin, Ch. Sh.; Manatbev, R.K.; Yersina, A. K.; Tulepbergenov, A. K.

2012-01-01

The report presents the results of research and development on of promising wind units carousel type with a high ratio utilization of wind energy. This devices use a well-known invention – the wind turbine Darrieus. The rotation of the turbine is due to the action of ascensional power to aerodynamic well-streamlined symmetrical about the chord wing profiles of NASA, which are working wind turbine blades. The shaft rotation can be connected with the working blades of one of two ways: using the “swings” or the way “troposkino”. Darrieus turbine has a ratio utilization of wind energy xmax=045. Despite the fact that this is a good indicator of the efficiency of the turbine working, the proposed option allows us to significantly increase the value of this coefficient. The bases methodology of this research is a method of technical and technological research and development design of prospective wind energy construction (WES). Key words: wind turbine, the blade, coefficient utilization of wind energy

Genetic architecture of retinal and macular degenerative diseases: the promise and challenges of next-generation sequencing

Science.gov (United States)

2013-01-01

Inherited retinal degenerative diseases (RDDs) display wide variation in their mode of inheritance, underlying genetic defects, age of onset, and phenotypic severity. Molecular mechanisms have not been delineated for many retinal diseases, and treatment options are limited. In most instances, genotype-phenotype correlations have not been elucidated because of extensive clinical and genetic heterogeneity. Next-generation sequencing (NGS) methods, including exome, genome, transcriptome and epigenome sequencing, provide novel avenues towards achieving comprehensive understanding of the genetic architecture of RDDs. Whole-exome sequencing (WES) has already revealed several new RDD genes, whereas RNA-Seq and ChIP-Seq analyses are expected to uncover novel aspects of gene regulation and biological networks that are involved in retinal development, aging and disease. In this review, we focus on the genetic characterization of retinal and macular degeneration using NGS technology and discuss the basic framework for further investigations. We also examine the challenges of NGS application in clinical diagnosis and management. PMID:24112618

A New Nonsense Mutation in CDKL5 Gene in a Male Patient with Early Onset Refractory Epilepsy: a Case Report

Directory of Open Access Journals (Sweden)

Soudeh Ghafouri-Fard

2016-02-01

Full Text Available Background The X-linked cyclin-dependent kinase like 5 (CDKL5/STK9 gene has been shown to be responsible for a severe encephalopathy condition characterized by early onset of epilepsy and severe developmental delay. CDKL5 mutations have been shown to be more frequent among female patients. Results Here we report a 6- month male patient, second child of a healthy non consanguineous in the Iranian population. He has been affected by early onset epileptic refractory seizures and developmental delay. Whole-exome sequencing (WES has revealed a base substitution c.173T>A in CDKL5 gene, resulting in the formation of stop codon p.L58X. This mutation resides in the catalytic domain of the corresponding protein and is expected to result in premature RNA break down with no CDKL5 resulting protein. Conclusion   The present report highlights the importance of CDKL5 mutation analysis in male patients affected with early onset refractory epilepsy.

Python for data analysis data wrangling with Pandas, NumPy, and IPython

CERN Document Server

McKinney, Wes

2017-01-01

Get complete instructions for manipulating, processing, cleaning, and crunching datasets in Python. Updated for Python 3.6, the second edition of this hands-on guide is packed with practical case studies that show you how to solve a broad set of data analysis problems effectively. You’ll learn the latest versions of pandas, NumPy, IPython, and Jupyter in the process. Written by Wes McKinney, the creator of the Python pandas project, this book is a practical, modern introduction to data science tools in Python. It’s ideal for analysts new to Python and for Python programmers new to data science and scientific computing. Data files and related material are available on GitHub. Use the IPython shell and Jupyter notebook for exploratory computing Learn basic and advanced features in NumPy (Numerical Python) Get started with data analysis tools in the pandas library Use flexible tools to load, clean, transform, merge, and reshape data Create informative visualizations with matplotlib ...

Determination of water environment standards based on water quality criteria in China: Limitations and feasibilities.

Science.gov (United States)

Wang, Tieyu; Zhou, Yunqiao; Bi, Cencen; Lu, Yonglong; He, Guizhen; Giesy, John P

2017-07-01

There is a need to formulate water environment standards (WESs) from the current water quality criteria (WQC) in China. To this end, we briefly summarize typical mechanisms applied in several countries with longer histories of developing WESs, and three limitations to formulating WESs in China were identified. After analyzing the feasibility factors including economic development, scientific support capability and environmental policies, we realized that China is still not ready for a complete change from its current nation-wide unified WES system to a local-standard-based system. Thus, we proposed a framework for transformation from WQC to WESs in China. The framework consists of three parts, including responsibilities, processes and policies. The responsibilities include research authorization, development of guidelines, and collection of information, at both national and local levels; the processes include four steps and an impact factor system to establish water quality standards; and the policies include seven specific proposals. Copyright © 2016. Published by Elsevier B.V.

Copper Disk Manufactured at the Space Optics Manufacturing and Technology Center

Science.gov (United States)

2001-01-01

This photograph shows Wes Brown, Marshall Space Flight Center's (MSFC's) lead diamond tuner, an expert in the science of using diamond-tipped tools to cut metal, inspecting the mold's physical characteristics to ensure the uniformity of its more than 6,000 grooves. This king-size copper disk, manufactured at the Space Optics Manufacturing and Technology Center (SOMTC) at MSFC, is a special mold for making high resolution monitor screens. This master mold will be used to make several other molds, each capable of forming hundreds of screens that have a type of lens called a fresnel lens. Weighing much less than conventional optics, fresnel lenses have multiple concentric grooves, each formed to a precise angle, that together create the curvature needed to focus and project images. The MSFC leads NASA's space optics manufacturing technology development as a technology leader for diamond turning. The machine used to manufacture this mold is among many one-of-a-kind pieces of equipment of MSFC's SOMTC.

Environmental investigations at the Paducah Gaseous Diffusion Plant and surrounding area, McCracken County, Kentucky. Volume 1 - Executive summary. Final report

International Nuclear Information System (INIS)

1994-05-01

This report details the results of four studies into environmental and cultural resources on and near the Department of Energy's (DOE) Paducah Gaseous Diffusion Plant (PGDP) located in Western Kentucky in McCracken County, approximately 10 miles west of Paducah, KY. The area investigated includes the PGDP facility proper, additional area owned by DOE under use permit to the Western Kentucky Wildlife Management Area (WKWMA), area owned by the Commonwealth of Kentucky that is administered by the WKWMA, area owned by the Tennessee Valley Authority (TVA), the Metropolis Lake State Nature preserve and some privately held land. DOE requested the assistance and support of the US Army Engineer District, Nashville (CEORN) in conducting various environmental investigations of the area. The US Army Engineer Waterways Experiment Station (WES) provided technical support to the CEORN for environmental investigations of (1) wetland resources, (2) threatened or endangered species and habitats, and (3) cultural resources. A floodplain investigation was conducted by CEORN

Air pollution control residues from waste incineration: current UK situation and assessment of alternative technologies.

Science.gov (United States)

Rani, D Amutha; Boccaccini, A R; Deegan, D; Cheeseman, C R

2008-11-01

Current disposal options for APC residues in the UK and alternative treatment technologies developed world-wide have been reviewed. APC residues are currently landfilled in the UK where they undergo in situ solidification, although the future acceptability of this option is uncertain because the EU waste acceptance criteria (WAC) introduce strict limits on leaching that are difficult to achieve. Other APC residue treatment processes have been developed which are reported to reduce leaching to below relevant regulatory limits. The Ferrox process, the VKI process, the WES-PHix process, stabilisation/solidification using cementitious binders and a range of thermal treatment processes are reviewed. Thermal treatment technologies convert APC residues combined with other wastes into inert glass or glass-ceramics that encapsulate heavy metals. The waste management industry will inevitably use the cheapest available option for treating APC residues and strict interpretation and enforcement of waste legislation is required if new, potentially more sustainable technologies are to become commercially viable.

Air pollution control residues from waste incineration: Current UK situation and assessment of alternative technologies

International Nuclear Information System (INIS)

Amutha Rani, D.; Boccaccini, A.R.; Deegan, D.; Cheeseman, C.R.

2008-01-01

Current disposal options for APC residues in the UK and alternative treatment technologies developed world-wide have been reviewed. APC residues are currently landfilled in the UK where they undergo in situ solidification, although the future acceptability of this option is uncertain because the EU waste acceptance criteria (WAC) introduce strict limits on leaching that are difficult to achieve. Other APC residue treatment processes have been developed which are reported to reduce leaching to below relevant regulatory limits. The Ferrox process, the VKI process, the WES-PHix process, stabilisation/solidification using cementitious binders and a range of thermal treatment processes are reviewed. Thermal treatment technologies convert APC residues combined with other wastes into inert glass or glass-ceramics that encapsulate heavy metals. The waste management industry will inevitably use the cheapest available option for treating APC residues and strict interpretation and enforcement of waste legislation is required if new, potentially more sustainable technologies are to become commercially viable

Histochemical Comparison of the Hypopharyngeal Gland in Apis cerana Fabricius, 1793 Workers and Apis mellifera Linnaeus, 1758 Workers

Directory of Open Access Journals (Sweden)

Guntima Suwannapong

2010-01-01

Full Text Available Hypopharyngeal glands of honeybee are age-dependent structures that change with the size of acini and are correlated with various social behaviors. The histochemical structure of Apis cerana and A. mellifera worker hypopharyngeal glands in four different developmental stages wes stained with ninhydrin Schiff's and periodic acid Schiff's reagents (PAS for localization of proteins and carbohydrates, respectively, and examined with light microscopy. Nurse bees of both honeybee species had significantly larger glands as compared to guards and forgers, but there were no statistically significant differences between these two species after accounting for caste. Gland protein concentration increased progressively in nurse bees, and this was correlated with the appearance of enriched protein granules in the cytoplasm. In addition, the hypopharyngeal gland protein concentration of A. mellifera was higher than that of A. cerana even though gland size was not significantly different between species. However, gland size was shown to have decreased progressively in foragers and guards.

Genetic diversity studies in twenty accessions of hot pepper (Capsicum spp L.) in Ghana

International Nuclear Information System (INIS)

Doku, S.K.

2015-07-01

Twenty (20) accessions of hot pepper (Capsicum spp L.) were collected from eight geographical regions of Ghana for genetic diversity studies. The objective was to assess genetic relationship among them using phenotypic and molecular traits and to evaluate their elemental composition. A replicated field experiment was conducted to assess their genetic diversity based on 13 quantitative traits and 22 qualitative traits using the IBPGR descriptor list for Capsicum. Confirmation of their identities was done using 10 SSR markers. The accessions were also evaluated for macro, micro and trace elements in their fresh fruits using the Instrumental Neutron Activation Analysis (INAA). Five essential macro elements (Ca, Cl, K, Mg and Na), two micro elements (Al and Mn) and one trace element (Br) were detected by INAA. Results from the agromorphological study revealed that accession Wes 01 had the widest stem width, matured leaf width, high fruit set but late maturing. Nor 03 was early maturing and had high fruit set, but also possessed the highest number of seeds per fruit. Fruit weight, fruit width, fruit length and plant canopy width, recorded the highest variabilities with 66.191; 53.24; 49.32; and 32.42 coefficients of variation (CVs), respectively. Few traits such as plant canopy width, plant height, fruit length, mature leaf length and number of seeds per fruit contributed substantially to total genetic variance as revealed by the principal component analysis (PCA). A dendrogram generated using morphological traits grouped accessions into cultivated and wild genotypes of pepper and all the accessions were identified as separate entities with no duplications. Strong correlation was recorded between plant canopy width and plant height, mature leaf length and mature leaf width, and also fruit weight and fruit width and fruit length. Negative correlation was however, observed between fruit length and days to 50% fruiting and flowering. All three accessions from the Northern

Evaluation of the influence of implant placement timing on the esthetic outcomes of single tooth implant treatment in the anterior maxilla: A retrospective study.

Science.gov (United States)

Arora, Himanshu; Ivanovski, Saso

2018-05-15

The purpose of this retrospective study was to investigate the influence of implant placement timing on the esthetic outcomes for single implants in the anterior maxilla. One hundred and ten patients (48 males; 62 females) who received a single-tooth implant after extraction either immediately (Type 1); after 4-8 weeks (Type 2); after 8-16 weeks (Type 3); or more than 16 weeks (Type 4) were evaluated in terms of esthetic outcomes after a mean post-placement interval of 26.3 months (range 12-116). Esthetic outcomes were measured using the Pink and White Esthetic Score (PES; WES). Stepwise regression analysis was performed to analyze the effect of timing of placement, as well as patient demographics and other clinical parameters on the esthetic outcomes. No statistically significantly differences in PES were found between the various treatment modalities with Type 1 implants (n = 33) scoring 10.58 ± 1.65 (median: 11), followed by 10.36 ± 2.09 (median: 10.5), 9.68 ± 2.43 (median: 10), and 9.63 ± 2.21 (median: 10) for Type 2 (n = 14), Type 3 (n = 19), and Type 4 (n = 44), respectively. For immediate implants, a trend towards better esthetic outcomes was observed when implant placement was done flaplessly in cases with intact buccal bone (Type 1A, median PES 11) as compared to cases with partial/complete missing buccal plates where a flap was raised (Type 1B, median PES 10). Overall, the only parameter that influenced esthetic outcomes (as measured by PES) was gender, with females having significantly superior results. The median WES was 8 and 96% of the crowns were deemed esthetically acceptable, with crowns placed by specialist prosthodontists yielding higher scores than those placed by general practitioners. Single tooth implants in the anterior maxilla showed satisfactory outcomes when measured with objective esthetic criteria. Timing of implant placement did not significantly influence the esthetic outcomes, although a trend

Engaging a Community for Rare Genetic Disease: Best Practices and Education From Individual Crowdfunding Campaigns.

Science.gov (United States)

Ortiz, Romina Alicia; Witte, Steven; Gouw, Arvin; Sanfilippo, Ana; Tsai, Richard; Fumagalli, Danielle; Yu, Christine; Lant, Karla; Lipitz, Nicole; Shepphird, Jennifer; Alvina, Fidelia B; Cheng-Ho Lin, Jimmy

2018-02-05

Genetic sequencing is critically important to diagnostic health care efforts in the United States today, yet it is still inaccessible to many. Meanwhile, the internet and social networking have made crowdfunding a realistic avenue for individuals and groups hoping to fund medical and research causes, including patients in need of whole exome genetic sequencing (WES). Amplify Hope is an educational program designed to investigate what factors affect the success of medical crowdfunding campaigns. We conducted a needs assessment, a series of 25 interviews concerning crowdfunding, and provided training on best practices identified through our assessment for 11 individuals hoping to run their medical crowdfunding campaigns to raise money for patients to access trio WES to identify the mutated proteins that caused their apparent inherited disease. The crowdfunding education was given in a 30-day training period with resources such as webinars, fact sheets and a crowdfunding training guide emailed to each participant. All campaigns were launched on the same date and were given 30 days to raise the same goal amount of US $5000. Reviewing the 4 crowdfunding campaigns that raised the goal amount within the 30-day period, we sought to identify features that made the 4 crowdfunding campaigns successful. In addition, we sought to assess which factors the resulting 75 donors report as influencing their decision to donate to a campaign. Finally, we investigated whether crowdfunding campaigns for exome sequencing had an impact on increasing applicant's and donors' knowledge of genomics. Of the 86 study inquiries, 11 participants submitted the required forms and launched their crowdfunding campaigns. A total of 4 of the 11 campaigns raised their goal amounts within 30 days. We found that social media played an important role in all campaigns. Specifically, a strong social media network, an active outreach process to networks, as well as engagement within the study all correlated

Space Transportation System Liftoff Debris Mitigation Process Overview

Science.gov (United States)

Mitchell, Michael; Riley, Christopher

2011-01-01

Liftoff debris is a top risk to the Space Shuttle Vehicle. To manage the Liftoff debris risk, the Space Shuttle Program created a team with in the Propulsion Systems Engineering & Integration Office. The Shutt le Liftoff Debris Team harnesses the Systems Engineering process to i dentify, assess, mitigate, and communicate the Liftoff debris risk. T he Liftoff Debris Team leverages off the technical knowledge and expe rtise of engineering groups across multiple NASA centers to integrate total system solutions. These solutions connect the hardware and ana lyses to identify and characterize debris sources and zones contribut ing to the Liftoff debris risk. The solutions incorporate analyses sp anning: the definition and modeling of natural and induced environmen ts; material characterizations; statistical trending analyses, imager y based trajectory analyses; debris transport analyses, and risk asse ssments. The verification and validation of these analyses are bound by conservative assumptions and anchored by testing and flight data. The Liftoff debris risk mitigation is managed through vigilant collab orative work between the Liftoff Debris Team and Launch Pad Operation s personnel and through the management of requirements, interfaces, r isk documentation, configurations, and technical data. Furthermore, o n day of launch, decision analysis is used to apply the wealth of ana lyses to case specific identified risks. This presentation describes how the Liftoff Debris Team applies Systems Engineering in their proce sses to mitigate risk and improve the safety of the Space Shuttle Veh icle.

Kvintilianas apie iškalbos privalumus | Quintilian: on the virtues of eloquence

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Rasa Valienė

2007-01-01

Full Text Available In the Institutio Oratoria of Quintilian we find a presentation of a theory of the virtues of eloquence: purity of language (latinitas, clarity (perspicuitas, appropriateness (aptum and ornament (ornatus. All of them were originated by earlier Greek philosophers Aristotle and Theophrastus. Later this theory was taken on and elaborated by Roman rhetoricians – Cicero and Quintilian. Aristotle in his Rhetoric explicitly identified three of the four virtues (clarity, appropriateness and correctness. Theophrastus created a theory of four virtues of eloquence (correctness, clarity, appropriateness and ornament. His system was adopted by most of others. Dionysius, however, developed the most complex system of virtues. He presented a theory of virtues, which were divided into necessary (purity of language, appropriateness, lucidity and brevity and accessory ones. The accessory virtues were further subdivided into another three groups. Rhetorica ad Herennium offered a three fold system: elegantia (including both correctness and clarity, compositio (similar to appropriateness and diginitas (similar to ornament. Basically, in almost all aspects being closer to Cicero (who continues the tradition of Theophrastus, Quintilian is more focused on his theory of eloquence. He discusses the virtues of eloquence very widely and deeply, step by step, drawing a number of examples and including the educational process of an orator. Above all, although the theory of four virtues of Quintilian has been influenced by Ciceron, to some extent in general it does not claim originality and plays a paramount role in modern rhetorics, stylistic and pedagogy.

Early-stage squamous cell carcinoma of the oropharynx: Radiotherapy vs. Trans-Oral Robotic Surgery (ORATOR) – study protocol for a randomized phase II trial

International Nuclear Information System (INIS)

Nichols, Anthony C; Kuruvilla, Sara; Chen, Jeff; Corsten, Martin; Odell, Michael; Eapen, Libni; Theurer, Julie; Doyle, Philip C; Wehrli, Bret; Kwan, Keith; Palma, David A; Yoo, John; Hammond, J Alex; Fung, Kevin; Winquist, Eric; Read, Nancy; Venkatesan, Varagur; MacNeil, S Danielle; Ernst, D Scott

2013-01-01

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has markedly increased over the last three decades due to newly found associations with human papillomavirus (HPV) infection. Primary radiotherapy (RT) is the treatment of choice for OPSCC at most centers, and over the last decade, the addition of concurrent chemotherapy has led to a significant improvement in survival, but at the cost of increased acute and late toxicity. Transoral robotic surgery (TORS) has emerged as a promising alternative treatment, with preliminary case series demonstrating encouraging oncologic, functional, and quality of life (QOL) outcomes. However, comparisons of TORS and RT in a non-randomized fashion are susceptible to bias. The goal of this randomized phase II study is to compare QOL, functional outcomes, toxicity profiles, and survival following primary RT (± chemotherapy) vs. TORS (± adjuvant [chemo] RT) in patients with OPSCC. The target patient population comprises OPSCC patients who would be unlikely to require chemotherapy post-resection: Tumor stage T1-T2 with likely negative margins at surgery; Nodal stage N0-2, ≤3 cm in size, with no evidence of extranodal extension on imaging. Participants will be randomized in a 1:1 ratio between Arm 1 (RT ± chemotherapy) and Arm 2 (TORS ± adjuvant [chemo] RT). In Arm 1, patients with N0 disease will receive RT alone, whereas N1-2 patients will receive concurrent chemoradiation. In Arm 2, patients will undergo TORS along with selective neck dissections, which may be staged. Pathologic high-risk features will be used to determine the requirement for adjuvant radiotherapy +/- chemotherapy. The primary endpoint is QOL score using the M.D. Anderson Dysphagia Inventory (MDADI), with secondary endpoints including survival, toxicity, other QOL outcomes, and swallowing function. A sample of 68 patients is required. This study, if successful, will provide a much-needed randomized comparison of the conventional strategy of primary RT vs. the novel strategy of primary TORS. The trial is designed to provide a definitive QOL comparison between the two arms, and to inform the design of an eventual phase III trial for survival outcomes. http://www.clinicaltrials.gov/ct2/show/NCT01590355?term

Pathway to a paradigm: the linear nonthreshold dose-response model in historical context. The American Academy of Health Physics 1995 Radiology Centennial Hartman Oration.

Science.gov (United States)

Kathren, R L

1996-05-01

This paper traces the evolution of the linear nonthreshold dose-response model and its acceptance as a paradigm in radiation protection practice and risk analysis. Deterministic effects such as skin burns and even deep tissue trauma were associated with excessive exposure to x rays shortly after their discovery, and carcinogenicity was observed as early as 1902. Still, it was not until 1925 that the first protective limits were suggested. For three decades these limits were based on the concept of a tolerance dose which, if not exceeded, would result in no demonstrable harm to the individual and implicitly assumed a threshold dose below which radiation effects would be absent. After World War II, largely because of genetic concerns related to atmospheric weapons testing, radiation protection dose limits were expressed in terms of a risk based maximum permissible dose which clearly implied no threshold. The 1927 discovery by Muller of x-ray induced genetic mutations in fruit flies, linear with dose and with no apparent threshold, was an important underpinning of the standards. The linear nonthreshold dose-response model was originally used to provide an upper limit estimate of the risk, with zero being the lower limit, of low level irradiation since the dose-response curve could not be determined at low dose levels. Evidence to the contrary such as hormesis and the classic studies of the radium dial painters notwithstanding, the linear nonthreshold model gained greater acceptance and in the centennial year of the discovery of x rays stands as a paradigm although serious questions are beginning to be raised regarding its general applicability. The work includes a brief digression describing the work of x-ray protection pioneer William Rollins and concludes with a recommendation for application of a de minimis dose level in radiation protection.

Saskoil annual report 1992

International Nuclear Information System (INIS)

1993-01-01

Saskoil is a publicly traded oil and gas company in Saskatchewan with productive properties located in western Canada. This document presents a review of the year's activities, with production-related statistics and financial statements included. Highlights of 1992 include production of 240 million ft 3 /d of natural gas, about the same as in 1991, and crude oil sales of 39,800 bbl/d compared to 32,700 bbl/d in 1991. Saskoil participated in drilling 63 oil wells, including 28 horizontal wells, and 19 natural gas wells. Saskoil's marketing subsidary Wes Cana Energy Marketing increased its third-party crude oil sales by 52% to 37,300 bbl/d and its third-party natural gas volumes by 35% to 182.6 million ft 3 /d compared to 1991. Total proven and probable reserves at the end of 1992 reached 208.9 million bbl for crude oil and natural gas liquids, and 1,273.7 billion ft 3 of natural gas. Revenue loss for the year ended December 31, 1992 was $39 million, compared to a 1991 loss of $74.9 million. 7 tabs

Occurrence, production, and export of lipophilic compounds by hydrocarbonoclastic marine bacteria and their potential use to produce bulk chemicals from hydrocarbons.

Science.gov (United States)

Manilla-Pérez, Efraín; Lange, Alvin Brian; Hetzler, Stephan; Steinbüchel, Alexander

2010-05-01

Petroleum (or crude oil) is a complex mixture of hydrocarbons. Annually, millions of tons of crude petroleum oil enter the marine environment from either natural or anthropogenic sources. Hydrocarbon-degrading bacteria (HDB) are able to assimilate and metabolize hydrocarbons present in petroleum. Crude oil pollution constitutes a temporary condition of carbon excess coupled to a limited availability of nitrogen that prompts marine oil-degrading bacteria to accumulate storage compounds. Storage lipid compounds such as polyhydroxyalkanoates (PHAs), triacylglycerols (TAGs), or wax esters (WEs) constitute the main accumulated lipophilic substances by bacteria under such unbalanced growth conditions. The importance of these compounds as end-products or precursors to produce interesting biotechnologically relevant chemicals has already been recognized. In this review, we analyze the occurrence and accumulation of lipid storage in marine hydrocarbonoclastic bacteria. We further discuss briefly the production and export of lipophilic compounds by bacteria belonging to the Alcanivorax genus, which became a model strain of an unusual group of obligate hydrocarbonoclastic bacteria (OHCB) and discuss the possibility to produce neutral lipids using A. borkumensis SK2.

Genomic Landscape Survey Identifies SRSF1 as a Key Oncodriver in Small Cell Lung Cancer.

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Liyan Jiang

2016-04-01

Full Text Available Small cell lung cancer (SCLC is an aggressive disease with poor survival. A few sequencing studies performed on limited number of samples have revealed potential disease-driving genes in SCLC, however, much still remains unknown, particularly in the Asian patient population. Here we conducted whole exome sequencing (WES and transcriptomic sequencing of primary tumors from 99 Chinese SCLC patients. Dysregulation of tumor suppressor genes TP53 and RB1 was observed in 82% and 62% of SCLC patients, respectively, and more than half of the SCLC patients (62% harbored TP53 and RB1 mutation and/or copy number loss. Additionally, Serine/Arginine Splicing Factor 1 (SRSF1 DNA copy number gain and mRNA over-expression was strongly associated with poor survival using both discovery and validation patient cohorts. Functional studies in vitro and in vivo demonstrate that SRSF1 is important for tumorigenicity of SCLC and may play a key role in DNA repair and chemo-sensitivity. These results strongly support SRSF1 as a prognostic biomarker in SCLC and provide a rationale for personalized therapy in SCLC.

Personalized In Vitro and In Vivo Cancer Models to Guide Precision Medicine

Science.gov (United States)

Pauli, Chantal; Hopkins, Benjamin D.; Prandi, Davide; Shaw, Reid; Fedrizzi, Tarcisio; Sboner, Andrea; Sailer, Verena; Augello, Michael; Puca, Loredana; Rosati, Rachele; McNary, Terra J.; Churakova, Yelena; Cheung, Cynthia; Triscott, Joanna; Pisapia, David; Rao, Rema; Mosquera, Juan Miguel; Robinson, Brian; Faltas, Bishoy M.; Emerling, Brooke E.; Gadi, Vijayakrishna K.; Bernard, Brady; Elemento, Olivier; Beltran, Himisha; Dimichelis, Francesca; Kemp, Christopher J.; Grandori, Carla; Cantley, Lewis C.; Rubin, Mark A.

2017-01-01

Precision Medicine is an approach that takes into account the influence of individuals' genes, environment and lifestyle exposures to tailor interventions. Here, we describe the development of a robust precision cancer care platform, which integrates whole exome sequencing (WES) with a living biobank that enables high throughput drug screens on patient-derived tumor organoids. To date, 56 tumor-derived organoid cultures, and 19 patient-derived xenograft (PDX) models have been established from the 769 patients enrolled in an IRB approved clinical trial. Because genomics alone was insufficient to identify therapeutic options for the majority of patients with advanced disease, we used high throughput drug screening effective strategies. Analysis of tumor derived cells from four cases, two uterine malignancies and two colon cancers, identified effective drugs and drug combinations that were subsequently validated using 3D cultures and PDX models. This platform thereby promotes the discovery of novel therapeutic approaches that can be assessed in clinical trials and provides personalized therapeutic options for individual patients where standard clinical options have been exhausted. PMID:28331002

Kritické zhodnocení Popperova řešení problému indukce

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Ondřej Sloup

2015-12-01

Full Text Available Is there any kind of justification fora belief that the future will be largely like the past? In the eighteenth century David Hume formulatedthe problem of induction in a similar spirit, andhis version is now conventional. Even two hundred and fifty years after Hume’s death, the ef-fort to justify inductive inferences still preoccupiesphilosophers. Sir Karl Popper believed that he hadsuccessfully solved this fundamental philosophicalproblem. The present article introduces the problematic situation formulated by David Hume, followed by Popper’s original solution to the problem. Along with that, relevant criticism from John Worall and Wes Salmon will be presented. It concentrates on Popper’s rejection of induction and therelated inability to implement any prediction aboutthe future within critical rationalism. The validityor failure of Popper’s solution is discussed towardsthe end of the article, together with a reconsideration of the current state of the debate. The lastpart of the study is devoted to the author’s proposal, which should be able to stand up againstanti-Popperian objections while remaining withinthe boundaries of critical-rationalist methodology.

Scream, cultura popular y el feminismo de la tercera ola: "Yo no soy mi madre"

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Kathleen Rowe Karlyn

2005-01-01

Full Text Available This paper analyzes Wes Craven’s horror trilogy Scream; the trilogy, like all popular texts, is riddled with contradictions about women’s representation that beg a careful analysis based on an informed understanding of media culture and representation, of history, and of the issues that matter to young women today. My reading of the film draws up the connections between Third Wave feminism and popular culture in order to show how these films provide a rich opportunity to study the contradictions and possibilities of feminism in a postmodern age. The purpose here is not to mount an unconditional defense of popular culture, but to argue that women who care about the next generation of girls need to learn more about the popular texts they're drawn to. If a productive conversation is going to happen among women of all ages about the future of the feminist movement, it will have to take place on the terrain of popular culture where young women today are refashioning feminism toward their own ends.

Whole Exome Sequencing Reveals Compound Heterozygosity for Ethnically Distinct PEX7 Mutations Responsible for Rhizomelic Chondrodysplasia Punctata, Type 1

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Jessie C. Jacobsen

2015-01-01

Full Text Available We describe two brothers who presented at birth with bone growth abnormalities, followed by development of increasingly severe intellectual and physical disability, growth restriction, epilepsy, and cerebellar and brain stem atrophy, but normal ocular phenotypes. Case 1 died at 19 years of age due to chronic respiratory illnesses without a unifying diagnosis. The brother remains alive but severely disabled at 19 years of age. Whole exome sequencing identified compound heterozygous stop mutations in the peroxisome biogenesis factor 7 gene in both individuals. Mutations in this gene cause rhizomelic chondrodysplasia punctata, type 1 (RCDP1. One mutation, p.Arg232∗, has only been documented once before in a Japanese family, which is of interest given these two boys are of European descent. The other mutation, p.Leu292∗, is found in approximately 50% of RCDP1 patients. These are the first cases of RCDP1 that describe the coinheritance of the p.Arg232∗ and p.Leu292∗ mutations and demonstrate the utility of WES in cases with unclear diagnoses.

Reference genotype and exome data from an Australian Aboriginal population for health-based research.

Science.gov (United States)

Tang, Dave; Anderson, Denise; Francis, Richard W; Syn, Genevieve; Jamieson, Sarra E; Lassmann, Timo; Blackwell, Jenefer M

2016-04-12

Genetic analyses, including genome-wide association studies and whole exome sequencing (WES), provide powerful tools for the analysis of complex and rare genetic diseases. To date there are no reference data for Aboriginal Australians to underpin the translation of health-based genomic research. Here we provide a catalogue of variants called after sequencing the exomes of 72 Aboriginal individuals to a depth of 20X coverage in ∼80% of the sequenced nucleotides. We determined 320,976 single nucleotide variants (SNVs) and 47,313 insertions/deletions using the Genome Analysis Toolkit. We had previously genotyped a subset of the Aboriginal individuals (70/72) using the Illumina Omni2.5 BeadChip platform and found ~99% concordance at overlapping sites, which suggests high quality genotyping. Finally, we compared our SNVs to six publicly available variant databases, such as dbSNP and the Exome Sequencing Project, and 70,115 of our SNVs did not overlap any of the single nucleotide polymorphic sites in all the databases. Our data set provides a useful reference point for genomic studies on Aboriginal Australians.

Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance

Science.gov (United States)

Roh, Whijae; Chen, Pei-Ling; Reuben, Alexandre; Spencer, Christine N.; Prieto, Peter A.; Miller, John P.; Gopalakrishnan, Vancheswaran; Wang, Feng; Cooper, Zachary A.; Reddy, Sangeetha M.; Gumbs, Curtis; Little, Latasha; Chang, Qing; Chen, Wei-Shen; Wani, Khalida; Petaccia De Macedo, Mariana; Chen, Eveline; Austin-Breneman, Jacob L.; Jiang, Hong; Roszik, Jason; Tetzlaff, Michael T.; Davies, Michael A.; Gershenwald, Jeffrey E.; Tawbi, Hussein; Lazar, Alexander J.; Hwu, Patrick; Hwu, Wen-Jen; Diab, Adi; Glitza, Isabella C.; Patel, Sapna P.; Woodman, Scott E.; Amaria, Rodabe N.; Prieto, Victor G.; Hu, Jianhua; Sharma, Padmanee; Allison, James P.; Chin, Lynda; Zhang, Jianhua; Wargo, Jennifer A.; Futreal, P. Andrew

2018-01-01

Immune checkpoint blockade produces clinical benefit in many patients. However better biomarkers of response are still needed, and mechanisms of resistance remain incompletely understood. To address this, we recently studied a cohort of melanoma patients treated with sequential checkpoint blockade against cytotoxic T lymphocyte antigen-4 (CTLA-4) followed by programmed death receptor-1 (PD-1), and identified immune markers of response and resistance. Building on these studies, we performed deep molecular profiling including T-cell receptor sequencing (TCR-seq) and whole exome sequencing (WES) within the same cohort, and demonstrated that a more clonal T cell repertoire was predictive of response to PD-1 but not CTLA-4 blockade. Analysis of copy number alterations identified a higher burden of copy number loss in non-responders to CTLA-4 and PD-1 blockade and found that it was associated with decreased expression of genes in immune-related pathways. The effect of mutational load and burden of copy number loss on response was non-redundant, suggesting the potential utility of a combinatorial biomarker to optimize patient care with checkpoint blockade therapy. PMID:28251903

Presidential Oration: The 18 th Annual Conference of the Indian Academy of Neurology, Trichi, Tamil Nadu, September 24-26, 2010, Epilepsy Care in Developing Countries

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Radhakrishnan Kurupath

2010-01-01

Full Text Available Nearly 80% of the 50 million people with epilepsy worldwide reside in developing countries that are least equipped to tackle the enormous medical, social and economic challenges posed by epilepsy. These include widespread poverty, illiteracy, inefficient and unevenly distributed health care systems, and social stigma and misconceptions associated with epilepsy. Several studies have reported that a large proportion of patients with epilepsy in developing countries never receive appropriate treatment for their condition, and many, though diagnosed and initiated on treatment, soon discontinue treatment. Unaffordable cost of treatment, unavailability of antiepileptic drugs, and superstitious and cultural beliefs contribute to high epilepsy treatment gap in resource-poor countries. A significant proportion of the current burden of epilepsy in developing countries can be minimized by educating the public about the positive aspects of life with epilepsy and the primary and secondary physicians about current trends in the management of epilepsies, scaling up routine availability of low-cost antiepileptic drugs, and developing cost-effective epilepsy surgery programs.

Small 'l' leadership.

Science.gov (United States)

Parsons, Jenni

2009-05-01

Recently I attended the RACGP Leadership Masterclass in Sydney. When I enrolled, I thought, 'Yes... sounds interesting...good speakers... I need to learn something about leadership...'As the time drew closer I started to get a bit anxious about the whole thing. I realised that the title, 'Masterclass', probably implied that the attendees were expected to already know something about leadership and its theories, if not have considerable expertise and experience in leadership. I also wondered how the workshop sessions were going to go and I started to feel a bit sorry for the facilitators. Imagine trying to facilitate a group of 10 aspiring leaders... a bit like trying to herd cats. A few days later I received a call from the organisers,saying they were a bit short of facilitators and could I help out if necessary. Great... better do a crash course in cat herding! Then there was the first 'predisposing activity'. Step 1: think of leaders you admire. Easy enough. Leaders of social justice and social change on a world stage, people who have shown great courage of their convictions and great orators popped into my head... Ghandi, Martin Luther King, Mandela, JFK. Step 2:describe the ways in which you are like these leaders. Whoa!Never going to measure up here. I wondered if there was going to be sessions on 'leadership for introverts', or 'leadership of small things', or 'leaders without grand vision or fabulous oratory skills', or perhaps 'leadership for people who are deeply suspicious of the corrupting influence of power'.

Datos para una biografía del jurista Pedro Murillo Velarde y Bravo

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Luis Díaz de la Guardia y López

2001-01-01

Full Text Available En el presente artículo se pretende aportar una serie de coordenadas para fijar la vida y el pensamiento de Pedro Murillo Velarde y Bravo (Laujar 1696-Puerto de Santa María 1753. Hidalgo de familia de caballeros, sobrino de un Obispo de Pamplona, rompe en principio con el entorno familiar de búsqueda de ascenso social para dedicarse a la misión en Filipinas, llegando a ser procurador provincial de la Compañía en Filipinas ante la Corte de Madrid y Roma. Gran jurista, tiistoriador, geógrafo, poeta, político y orador. Por medio de documentos y obras del autor no sólo se desentraña la vida del jesuíta sino también su pensamiento frente a las Filipinas, la política o la religión.This article intends to contribute a series of coordinates to establish the life and thinking of Pedro Murillo Velarde y Bravo (Laujuar 1696-Puerto de Santa María 1753. Noble from a family of gentlemen and nephew of a Bishop of Pamplona, firstly breaks away from the family environment that seeks social promotion to dedicate himself to the mission in the Philippines, becoming the Society of Jesus'provincial representative in the Philippines before the Court of Madrid and Rome. Great jurist, historian, geographer, poet, politician and orator. Through the documents and works of the autor, not only is the life of the Jesuit unravelled but also his thinking on the Philippines politics and religión.

The Piety of a noble woman in the light of Polish printed 17th century funeral speeches

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Urszula Kicińska

2012-12-01

Full Text Available 17th century funeral orations, as sources of didactic character, include numerous threads referring to the piety of baroque damsels. They are full of examples describing religiousness of women of virtually all ages and marital statuses (married, single and widowed. According to the model propagated by the clergy, a zealous catholic woman was supposed to be devoted to God and persistent in her belief. She should also worship Mary the Mother of God, Jesus and saint patrons, which was reflected in her participation in religious confraternities. It was also important that she attended religious services and pilgrimages as well as respected fasting periods and received holy sacraments. On every day basis, it was suggested that a God fearing Christian should live by the rules of the Decalogue, read religious books and contemplate the moment of death and prepare to it by reading ars bene moriendi guides. Charity work and generous donations to churches, monasteries, schools and homeless shelters were also important. Preachers also emphasised the personality features of a model catholic woman. Hence it was suggested that she should be hard working, reasonable, quiet and modest. Although clergymen emphasised deep and fervent religiousness of women whom they were describing in their sermons, we are actually unable to fully confirm the accuracy of their words. Therefore, it must be assumed that, on the one hand, this religiousness and piety was supposed to constitute an ideal role model, on the other hand, however, it resulted from the fear which accompanied people almost everywhere in turbulent times of the 17th century.

Individuals, institutions, and innovation in the debates of the French Revolution.

Science.gov (United States)

Barron, Alexander T J; Huang, Jenny; Spang, Rebecca L; DeDeo, Simon

2018-05-01

The French Revolution brought principles of "liberty, equality, fraternity" to bear on the day-to-day challenges of governing what was then the largest country in Europe. Its experiments provided a model for future revolutions and democracies across the globe, but this first modern revolution had no model to follow. Using reconstructed transcripts of debates held in the Revolution's first parliament, we present a quantitative analysis of how this body managed innovation. We use information theory to track the creation, transmission, and destruction of word-use patterns across over 40,000 speeches and a thousand speakers. The parliament as a whole was biased toward the adoption of new patterns, but speakers' individual qualities could break these overall trends. Speakers on the left innovated at higher rates, while speakers on the right acted to preserve prior patterns. Key players such as Robespierre (on the left) and Abbé Maury (on the right) played information-processing roles emblematic of their politics. Newly created organizational functions-such as the Assembly president and committee chairs-had significant effects on debate outcomes, and a distinct transition appears midway through the parliament when committees, external to the debate process, gained new powers to "propose and dispose." Taken together, these quantitative results align with existing qualitative interpretations, but also reveal crucial information-processing dynamics that have hitherto been overlooked. Great orators had the public's attention, but deputies (mostly on the political left) who mastered the committee system gained new powers to shape revolutionary legislation. Copyright © 2018 the Author(s). Published by PNAS.

Whole Exome Sequencing Leading to the Diagnosis of Dysferlinopathy with a Novel Missense Mutation (c.959G>C

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Abhisek Swaika

2016-01-01

Full Text Available Dysferlinopathy is an uncommon, progressive muscular dystrophy that has a wide phenotypic variability and primarily supportive management (Nguyen et al., 2007; Narayanaswami et al., 2014. Amyloid myopathy is a distinct, rare disorder that can present similarly to inflammatory myopathies and requires a high clinical suspicion for early intervention to prolong survival. Amyloid myopathy is typically associated with other systemic manifestations of amyloidosis, but rare cases of isolated amyloid myopathy have been described (Mandl et al., 2000; Hull et al., 2001. Positive Congo red stains on tissue biopsy remain the gold standard for diagnosis (Spuler et al., 1998; Karacostas et al., 2005. A high clinical suspicion and meticulous diagnostic workup that includes novel techniques are necessary for identifying these rare disorders. We report a middle-aged man with progressive leg muscle weakness who was initially treated as having amyloid myopathy but was later diagnosed as having dysferlinopathy by Whole Exome Sequencing (WES analysis. We also report a novel missense mutation (c.959G>C to help correlate in any patient with presumed dysferlinopathy and to add to the already known genotype of this disorder.

Measurement of the 243Am capture cross section at the n{sub T}OF facility; Medida de la sección eficaz de captura del 243Am en la instalación n{sub T}OF

Energy Technology Data Exchange (ETDEWEB)

Mendoza Cembranos, E.

2014-07-01

Nuclear data for minor actinides are necessary for improving the design and performance of advanced reactors and transmutation devices for the incineration of radioactive nuclear waste [Sal08, Gon09, Ali04, Ali06]. In particular, the 243Am isotope is relevant since it is the minor actinide which contributes more to the radiotoxicity of the nuclear waste between s3 03 and s3 04 years. In addition, the neutron capture in 243Am is the main gate to the creation of 244Cm and higher mass isotopes. The purpose of the this work is to provide experimental data on the 243Am(n, ) for improving the current evaluations. At present, there is no published neutron capture measurement of 243Am below 250 eV, and all the existing evaluations of the elastic and capture cross sections are based essentially on a single transmission measurement [Sim74]. Above 250 eV there are only a few capture measurements available [Wes85, Wis83], which show discrepancies that make them incompatible. Due to the lack of experimental data on 243Am the standard ENDF-6 format libraries present sizeable di rences between each other...(Author)

GRIN1 mutations cause encephalopathy with infantile-onset epilepsy, and hyperkinetic and stereotyped movement disorders.

Science.gov (United States)

Ohba, Chihiro; Shiina, Masaaki; Tohyama, Jun; Haginoya, Kazuhiro; Lerman-Sagie, Tally; Okamoto, Nobuhiko; Blumkin, Lubov; Lev, Dorit; Mukaida, Souichi; Nozaki, Fumihito; Uematsu, Mitsugu; Onuma, Akira; Kodera, Hirofumi; Nakashima, Mitsuko; Tsurusaki, Yoshinori; Miyake, Noriko; Tanaka, Fumiaki; Kato, Mitsuhiro; Ogata, Kazuhiro; Saitsu, Hirotomo; Matsumoto, Naomichi

2015-06-01

Recently, de novo mutations in GRIN1 have been identified in patients with nonsyndromic intellectual disability and epileptic encephalopathy. Whole exome sequencing (WES) analysis of patients with genetically unsolved epileptic encephalopathies identified four patients with GRIN1 mutations, allowing us to investigate the phenotypic spectrum of GRIN1 mutations. Eighty-eight patients with unclassified early onset epileptic encephalopathies (EOEEs) with an age of onset stereotypic hand movements were observed in two and three patients, respectively. All the four patients exhibited only nonspecific focal and diffuse epileptiform abnormality, and never showed suppression-burst or hypsarrhythmia during infancy. A de novo mosaic mutation (c.1923G>A) with a mutant allele frequency of 16% (in DNA of blood leukocytes) was detected in one patient. Three mutations were located in the transmembrane domain (3/4, 75%), and one in the extracellular loop near transmembrane helix 1. All the mutations were predicted to impair the function of the NMDA receptor. Clinical features of de novo GRIN1 mutations include infantile involuntary movements, seizures, and hand stereotypies, suggesting that GRIN1 mutations cause encephalopathy resulting in seizures and movement disorders. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Exome Sequencing and Linkage Analysis Identified Novel Candidate Genes in Recessive Intellectual Disability Associated with Ataxia.

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Jazayeri, Roshanak; Hu, Hao; Fattahi, Zohreh; Musante, Luciana; Abedini, Seyedeh Sedigheh; Hosseini, Masoumeh; Wienker, Thomas F; Ropers, Hans Hilger; Najmabadi, Hossein; Kahrizi, Kimia

2015-10-01

Intellectual disability (ID) is a neuro-developmental disorder which causes considerable socio-economic problems. Some ID individuals are also affected by ataxia, and the condition includes different mutations affecting several genes. We used whole exome sequencing (WES) in combination with homozygosity mapping (HM) to identify the genetic defects in five consanguineous families among our cohort study, with two affected children with ID and ataxia as major clinical symptoms. We identified three novel candidate genes, RIPPLY1, MRPL10, SNX14, and a new mutation in known gene SURF1. All are autosomal genes, except RIPPLY1, which is located on the X chromosome. Two are housekeeping genes, implicated in transcription and translation regulation and intracellular trafficking, and two encode mitochondrial proteins. The pathogenesis of these variants was evaluated by mutation classification, bioinformatic methods, review of medical and biological relevance, co-segregation studies in the particular family, and a normal population study. Linkage analysis and exome sequencing of a small number of affected family members is a powerful new technique which can be used to decrease the number of candidate genes in heterogenic disorders such as ID, and may even identify the responsible gene(s).

Making the most of RNA-seq: Pre-processing sequencing data with Opossum for reliable SNP variant detection [version 2; referees: 2 approved, 1 approved with reservations

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Laura Oikkonen

2017-03-01

Full Text Available Identifying variants from RNA-seq (transcriptome sequencing data is a cost-effective and versatile complement to whole-exome (WES and whole-genome sequencing (WGS analysis. RNA-seq (transcriptome sequencing is primarily considered a method of gene expression analysis but it can also be used to detect DNA variants in expressed regions of the genome. However, current variant callers do not generally behave well with RNA-seq data due to reads encompassing intronic regions. We have developed a software programme called Opossum to address this problem. Opossum pre-processes RNA-seq reads prior to variant calling, and although it has been designed to work specifically with Platypus, it can be used equally well with other variant callers such as GATK HaplotypeCaller. In this work, we show that using Opossum in conjunction with either Platypus or GATK HaplotypeCaller maintains precision and improves the sensitivity for SNP detection compared to the GATK Best Practices pipeline. In addition, using it in combination with Platypus offers a substantial reduction in run times compared to the GATK pipeline so it is ideal when there are only limited time or computational resources available.

A novel microfluidic origami photoelectrochemical sensor based on CdTe quantum dots modified molecularly imprinted polymer and its highly selective detection of S-fenvalerate

International Nuclear Information System (INIS)

Wang, Yanhu; Zang, Dejin; Ge, Shenguang; Ge, Lei; Yu, Jinghua; Yan, Mei

2013-01-01

Driven by the urgent demand of high-selectively point-of-care testing device for pesticide, molecular imprinting-photoelectrochemistry (MI-PEC) was introduced into microfluidic paper-based analytical strategy to design a novel paper-based photoelectrochemical (paper-based PEC) protocol. The MI-PEC strategy was constructed based on CdTe quantum dots dotted molecular imprinted polymers (CdTe QDs@MIPs), and triggered by a common ultraviolet lamp (∼365 nm, 50$). The paper-based PEC sensor was fabricated by immobilizing CdTe QDs@MIPs on paper-based screen-printed working electrodes (WEs) via gold nanoparticles (Au NPs), which was electrodeposited on the surface of WE to improve the electron transfer efficiency for high sensitivity. Using S-fenvalerate as model analyte, the produced photocurrent from the proposed paper-based MI-PEC sensor upon ultraviolet radiation decreased with the increasing concentrations of S-fenvalerate solution, and the quenched paper-based MI-PEC showed a low detection limit of 3.2 × 10 −9 mol L −1 . This study has made a successful attempt in the development of highly selective and sensitive photoelectrochemical sensor for S-fenvalerate monitoring

Genotype-phenotype correlations and expansion of the molecular spectrum of AP4M1-related hereditary spastic paraplegia

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Conceição Bettencourt

2017-11-01

Full Text Available Abstract Background Autosomal recessive hereditary spastic paraplegia (HSP due to AP4M1 mutations is a very rare neurodevelopmental disorder reported for only a few patients. Methods We investigated a Greek HSP family using whole exome sequencing (WES. Results A novel AP4M1A frameshift insertion, and a very rare missense variant were identified in all three affected siblings in the compound heterozygous state (p.V174fs and p.C319R; the unaffected parents were carriers of only one variant. Patients were affected with a combination of: (a febrile seizures with onset in the first year of life (followed by epileptic non-febrile seizures; (b distinctive facial appearance (e.g., coarse features, bulbous nose and hypomimia; (c developmental delay and intellectual disability; (d early-onset spastic weakness of the lower limbs; and (e cerebellar hypoplasia/atrophy on brain MRI. Conclusions We review genotype-phenotype correlations and discuss clinical overlaps between different AP4-related diseases. The AP4M1 belongs to a complex that mediates vesicle trafficking of glutamate receptors, being likely involved in brain development and neurotransmission.

A recognizable systemic connective tissue disorder with polyvalvular heart dystrophy and dysmorphism associated with TAB2 mutations.

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Ritelli, M; Morlino, S; Giacopuzzi, E; Bernardini, L; Torres, B; Santoro, G; Ravasio, V; Chiarelli, N; D'Angelantonio, D; Novelli, A; Grammatico, P; Colombi, M; Castori, M

2018-01-01

Deletions encompassing TAK1-binding protein 2 (TAB2) associated with isolated and syndromic congenital heart defects. Rare missense variants are found in patients with a similar phenotype as well as in a single individual with frontometaphyseal dysplasia. We describe a family and an additional sporadic patient with polyvalvular heart disease, generalized joint hypermobility and related musculoskeletal complications, soft, velvety and hyperextensible skin, short limbs, hearing impairment, and facial dysmorphism. In the first family, whole-exome sequencing (WES) disclosed the novel TAB2 c.1398dup (p.Thr467Tyrfs*6) variant that eliminates the C-terminal zinc finger domain essential for activation of TAK1 (TGFβ-activated kinase 1)-dependent signaling pathways. The sporadic case carryed a ~2 Mb de novo deletion including 28 genes also comprising TAB2. This study reveal an association between TAB2 mutations and a phenotype resembling Ehlers-Danlos syndrome with severe polyvalvular heart disease and subtle facial dysmorphism. Our findings support the existence of a wider spectrum of clinical phenotypes associated with TAB2 perturbations and emphasize the role of TAK1 signaling network in human development. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Current trend of annotating single nucleotide variation in humans--A case study on SNVrap.

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Li, Mulin Jun; Wang, Junwen

2015-06-01

As high throughput methods, such as whole genome genotyping arrays, whole exome sequencing (WES) and whole genome sequencing (WGS), have detected huge amounts of genetic variants associated with human diseases, function annotation of these variants is an indispensable step in understanding disease etiology. Large-scale functional genomics projects, such as The ENCODE Project and Roadmap Epigenomics Project, provide genome-wide profiling of functional elements across different human cell types and tissues. With the urgent demands for identification of disease-causal variants, comprehensive and easy-to-use annotation tool is highly in demand. Here we review and discuss current progress and trend of the variant annotation field. Furthermore, we introduce a comprehensive web portal for annotating human genetic variants. We use gene-based features and the latest functional genomics datasets to annotate single nucleotide variation (SNVs) in human, at whole genome scale. We further apply several function prediction algorithms to annotate SNVs that might affect different biological processes, including transcriptional gene regulation, alternative splicing, post-transcriptional regulation, translation and post-translational modifications. The SNVrap web portal is freely available at http://jjwanglab.org/snvrap. Copyright © 2014 Elsevier Inc. All rights reserved.

Polyamine stress at high pH in Escherichia coli K-12

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Tate Daniel P

2005-10-01

Full Text Available Abstract Background Polyamines such as spermine and spermidine are required for growth of Escherichia coli; they interact with nucleic acids, and they bind to ribosomes. Polyamines block porins and decrease membrane permeability, activities that may protect cells in acid. At high concentrations, however, polyamines impair growth. They impair growth more severely at high pH, probably due to their increased uptake as membrane-permeant weak bases. The role of pH is critical in understanding polyamine stress. Results The effect of polyamines was tested on survival of Escherichia coli K-12 W3110 in extreme acid or base (pH conditions outside the growth range. At pH 2, 10 mM spermine increased survival by 2-fold, and putrescine increased survival by 30%. At pH 9.8, however, E. coli survival was decreased 100-fold by 10 mM spermine, putrescine, cadaverine, or spermidine. At pH 8.5, spermine decreased the growth rate substantially, whereas little effect was seen at pH 5.5. Spermidine required ten-fold higher concentrations to impair growth. On proteomic 2-D gels, spermine and spermidine caused differential expression of 31 different proteins. During log-phase growth at pH 7.0, 1 mM spermine induced eight proteins, including PykF, GlpK, SerS, DeaD, OmpC and OmpF. Proteins repressed included acetate-inducible enzymes (YfiD, Pta, Lpd as well as RapA (HepA, and FabB. At pH 8.5, spermine induced additional proteins: TnaA, OmpA, YrdA and NanA (YhcJ and also repressed 17 proteins. Four of the proteins that spermine induced (GlpK, OmpA, OmpF, TnaA and five that were repressed (Lpd, Pta, SucB, TpiA, YfiD show similar induction or repression, respectively, in base compared to acid. Most of these base stress proteins were also regulated by spermidine, but only at ten-fold higher concentration (10 mM at high pH (pH 8.5. Conclusion Polyamines increase survival in extreme acid, but decrease E. coli survival in extreme base. Growth inhibition by spermine and

Learning charisma. Transform yourself into the person others want to follow.

Science.gov (United States)

Antonakis, John; Fenley, Marika; Liechti, Sue

2012-06-01

Many believe that charisma, the ability to captivate and inspire an audience, is innate. But through research in the laboratory and in the field, the authors, who all work at the University of Lausanne, have identified 2 tactics that help managers become more influential, trustworthy, and "leaderlike" in the eyes of others. Great orators and politicians employ these techniques instinctively, but anyone can learn how to use them. Nine of the tactics are verbal: metaphors, similes, and analogies; stories and anecdotes; contrasts; rhetorical questions; expressions of moral conviction; reflections of the group's sentiments; three-part lists; the setting of high goals; and conveying confidence that they can be achieved. Three are nonverbal: animated voice, facial expressions, and gestures. Though there are other tactics that leaders can use--repetition, humor, talking about sacrifice-the 12 singled out by the authors have the greatest effect and can work in almost any context. And the research shows that they also have a larger impact than strong presentation skills and speech structure. This article explores the 12 tactics in detail, providing examples from business and politics, and offers guidance on how to start implementing them. A manager's goal should be to incorporate them not only into public speaking but also into everyday interactions. They work because they help you create an emotional connection with your audience, even as they make you appear more powerful, competent, and worthy of respect. People who use them effectively will be able to unite their followers around a vision in a way that others can't. And in the authors' study, executives who practiced them saw the leadership scores that their audience gave them rise by about 60%.

Ocorrência de plantas daninhas no cultivo de beterraba com cobertura morta e adubação orgânica Weed occurrence in sugar beet crop under mulching and organic fertilization

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M.A.N Sediyama

2010-12-01

Full Text Available A cobertura do solo é prática importante na produção de hortaliças que também auxilia no controle de plantas daninhas. Praticamente, não existem pesquisas para o controle alternativo de plantas daninhas em beterraba, e são poucos os herbicidas indicados para a cultura. Neste trabalho, objetivou-se avaliar o efeito da cobertura do solo com palha de café ou bagaço de cana-de-açúcar e de doses de lodo de lagoa de decantação de águas residuárias de suinocultura na incidência de plantas daninhas e na produtividade de beterraba, cultivar Early Wonder. O experimento foi realizado na Fazenda Experimental da EPAMIG, em Oratórios-MG. Utilizou-se o esquema de parcelas subdivididas no delineamento experimental de blocos casualizados, com quatro repetições. Nas parcelas foram dispostos três tipos de cobertura do solo: bagaço de cana-de-açúcar, palha de café e ausência de cobertura, e nas subparcelas utilizaram-se cinco doses de lodo de lagoa de decantação de águas residuárias de suinocultura (0, 10, 20, 40 e 60 t ha-1. Aos 45 dias após o transplantio (DAT das mudas foi avaliada a população de plantas daninhas, e aos 70 DAT realizou-se a colheita. A palha de café e o bagaço de cana-de-açúcar foram eficazes na redução da massa fresca total das plantas daninhas, devido ao efeito supressor da cobertura morta sobre as dicotiledôneas. Todavia, a massa seca de tiririca aumentou com o uso de palha de café, enquanto a massa seca das outras monocotiledôneas não apresentou diferença entre os três tratamentos. O aumento das doses de lodo promoveu redução linear da massa seca de monocotiledôneas, exceto de tiririca. A cobertura com palha de café proporcionou maior massa unitária de raiz e maior produtividade de raízes comerciais, independentemente das doses de lodo.Soil covering is an important practice in vegetable production, also helping in weed control. There is almost no research involving alternative weed control

Sequential Path Analysis for Determination of Relationship Between Yield and Yield Components in Bread Wheat (Triticum aestivum.L.

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Mohtasham MOHAMMADI

2014-03-01

Full Text Available An experiment was conducted to evaluate 295 wheat genotypes in Alpha-Lattice design with two replications. The arithmetic mean and standard deviation of grain yield was 2706 and 950 (kg/ha,respectively. The results of correlation coefficients indicated that grain yield had significant and positive association with plant height, spike length, early growth vigor and agronomic score. Whereas there were negative correlation coefficients between grain yield and days to physiological maturity and canopy temperature before and during anthesis. Path analysis indicated agronomic score and plant height had high positive direct effects on grain yield, while canopy temperature before and during anthesis, and days to maturity, wes another trait having negative direct effect on grain yield. The results of sequential path analysis showed the traits that accounted as a criteria variable for high grain yield were agronomic score, plant height, canopy temperature, spike length, chlorophyll content and early growth vigor, which were determined as first, second and third order variables and had strong effects on grain yield via one or more paths. More important, as canopy temperature, agronomic score and early growth vigor can be evaluated quickly and easily, these traits may be used for evaluation of large populations.

ARL6IP6, a susceptibility locus for ischemic stroke, is mutated in a patient with syndromic Cutis Marmorata Telangiectatica Congenita.

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Abumansour, Iman S; Hijazi, Hadia; Alazmi, Anas; Alzahrani, Fatma; Bashiri, Fahad A; Hassan, Hamdy; Alhaddab, Mohammed; Alkuraya, Fowzan S

2015-08-01

Cutis Marmorata Telangiectatica Congenita (CMTC) is a congenital localized or generalized vascular anomaly, usually sporadic in occurrence. It can be associated with other cutaneous or systemic manifestations. About 300 cases have been reported. The molecular etiology remains largely unknown. The main purpose of this study is to delineate the molecular basis for a syndromic CMTC phenotype in a consanguineous Saudi family. Clinical phenotyping including detailed neurological imaging, followed by autozygosity mapping and trio whole exome sequencing (WES) are also studied. We have identified a homozygous truncating mutation in ARL6IP6 as the likely cause of a syndromic form of CMTC associated with major dysmorphism, developmental delay, transient ischemic attacks and cerebral vascular malformations. This gene was previously implicated by genome wide association study (GWAS) as a susceptibility locus to ischemic stroke in young adults. We identify ARL6IP6 as a novel candidate gene for a syndromic form of CMTC. This suggests that ischemic stroke or transient ischemic attacks (TIA) may represent, at least in some cases, the mild end of a phenotypic spectrum that has at its severe end autosomal recessive CMTC. This finding contributes to a growing appreciation of the continuum of Mendelian and common complex diseases.

Power system for production, construction, life support and operations in space

International Nuclear Information System (INIS)

Sovie, R.J.

1988-01-01

As one looks to man's future in space it becomes obvious that unprecedented amounts of power are required for the exploration, colonization, and exploitation of space. Activities envisioned include interplanetary travel and LEO to GEO transport using electric propulsion, Earth and lunar observatories, advance space stations, free-flying manufacturing platforms, communications platforms, and eventually evolutionary lunar and Mars bases. These latter bases would start as camps with modest power requirements (kWes) and evolve to large bases as manufacturing, food production, and life support materials are developed from lunar raw materials. These latter activities require very robust power supplies (MWes). The advanced power system technologies being pursued by NASA to fulfill these future needs are described. Technologies discussed will include nuclear, photovoltaic, and solar dynamic space power systems, including energy storage, power conditioning, power transmission, and thermal management. The state-of-the-art and gains to be made by technology advancements will be discussed. Mission requirements for a variety of applications (LEO, GEO, lunar, and Martian) will be treated, and data for power systems ranging from a few kilowatts to megawatt power systems will be represented. In addition the space power technologies being initiated under NASA's new Civilian Space Technology Initiative (CSTI) and Space Leadership Planning Group Activities will be discussed

Cloning and properties of the Salmonella typhimurium tricarboxylate transport operon in Escherichia coli

International Nuclear Information System (INIS)

Widenhorn, K.A.; Boos, W.; Somers, J.M.; Kay, W.W.

1988-01-01

The tricarboxylate transport operon (tctI) was cloned in Escherichia coli as a 12-kilobase (kb) fragment from an EcoRI library of the Salmonella typhimurium chromosome in λgtWES. It was further subcloned as a 12-kb fragment into pACYC184 and as an 8-kb fragment into pBR322. By insertional mutagenesis mediated by λTn5, restriction mapping, and phenotypic testing, the tctI operon was localized to a 4.5-kb region. The tctC gene which encodes a periplasmic binding protein (C-protein) was located near the center of the insert. E. coli/tctI clones on either multicopy or single-copy vectors grew on the same tricarboxylates as S. typhimurium, although unusually long growth lags were observed. E. coli/tctI clones exhibited similar [ 14 C] fluorocitrate transport kinetics to those of S. typhimurium, whereas E. coli alone was virtually impermeable to [ 14 C] fluorocitrate. The periplasmic C proteins (C1 and C2 isoelectric forms) were produced in prodigious quantities from the cloned strains. Motile E. coli/tctI clones were not chemotactic toward citrate, whereas tctI deletion mutants of S. typhimurium were. Taken together, these observations indicate that tctI is not an operon involved in chemotaxis

Identification of Novel Compound Mutations in PLA2G6-Associated Neurodegeneration Patient with Characteristic MRI Imaging.

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Guo, Sen; Yang, Liu; Liu, Huijie; Chen, Wei; Li, Jinchen; Yu, Ping; Sun, Zhong Sheng; Chen, Xiang; Du, Jie; Cai, Tao

2017-08-01

Neurodegeneration with brain iron accumulation comprises a heterogeneous group of disorders characterized clinically by progressive motor dysfunction. Accurate identification of de novo and rare inherited mutations is important for determining causative genes of undiagnosed neurological diseases. In the present study, we report a unique case with cerebellar ataxia symptoms and social communication difficulties in an intermarriage family. MRI showed a marked cerebellar atrophy and the "eye-of-the-tiger"-like sign in the medial globus pallidus. Potential genetic defects were screened by whole-exome sequencing (WES) for the patient and four additional family members. A previously undescribed de novo missense mutation (c.1634A>G, p.K545R) in the exon 12 of the PLA2G6 gene was identified. A second rare variant c.1077G>A at the end of exon 7 was also identified, which was inherited from the mother, and resulted in a frame-shift mutation (c.1074_1077del.GTCG) due to an alternative splicing. In conclusion, the identification of the "eye-of-the-tiger"-like sign in the globus pallidus of the patient expands the phenotypic spectrum of PLA2G6-associated disorders and reveals its value in differential diagnosis of PLA2G6-associated disorders.

Biallelic UNC80 mutations caused infantile hypotonia with psychomotor retardation and characteristic facies 2 in two Chinese patients with variable phenotypes.

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He, Yunjuan; Ji, Xing; Yan, Hui; Ye, Xiantao; Liu, Yu; Wei, Wei; Xiao, Bing; Sun, Yu

2018-06-20

Biallelic UNC80 mutations cause infantile hypotonia with psychomotor retardation and characteristic facies 2 (IHPRF2), which is characterized by hypotonia, developmental delay (DD)/intellectual disability (ID), intrauterine growth retardation, postnatal growth retardation and characteristic facial features. We report two unrelated Chinese patients with compound heterozygous UNC80 mutations inherited from their parents, as identified by whole-exome sequencing (WES). Mutations c.3719G>A (p.W1240*)/c.4926_4937del (p.N1643_L1646del) and c.4963C>T (p.R1655C)/c.8385C>G (p.Y2795*) were identified in patient 1 and patient 2, respectively. Although both patients presented with DD/ID and hypotonia, different manifestations also occurred. Patient 1 presented with infantile hypotonia, epilepsy and hyperactivity without growth retardation, whereas patient 2 presented with persistent hypotonia, growth retardation and self-injury without epilepsy. Furthermore, we herein summarize the genotypes and phenotypes of patients with UNC80 mutations reported in the literature, revealing that IHPRF2 is a phenotypically heterogeneous disease. Common facial dysmorphisms include a thin upper lip, a tented upper lip, a triangular face, strabismus and microcephaly. To some extent, the manifestations of IHPRF2 mimic those of Angelman syndrome (AS)-like syndromes. Copyright © 2018 Elsevier B.V. All rights reserved.

Gonadal mosaicism in ARID1B gene causes intellectual disability and dysmorphic features in three siblings.

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Ben-Salem, Salma; Sobreira, Nara; Akawi, Nadia A; Al-Shamsi, Aisha M; John, Anne; Pramathan, Thachillath; Valle, David; Ali, Bassam R; Al-Gazali, Lihadh

2016-01-01

The gene encoding the AT-rich interaction domain-containing protein 1B (ARID1B) has recently been shown to be one of the most frequently mutated genes in patients with intellectual disability (ID). The phenotypic spectrums associated with variants in this gene vary widely ranging for mild to severe non-specific ID to Coffin-Siris syndrome. In this study, we evaluated three children from a consanguineous Emirati family affected with ID and dysmorphic features. Genomic DNA from all affected siblings was analyzed using CGH array and whole-exome sequencing (WES). Based on a recessive mode of inheritance, homozygous or compound heterozygous variants shared among all three affected children could not be identified. However, further analysis revealed a heterozygous variant (c.4318C>T; p.Q1440*) in the three affected children in an autosomal dominant ID causing gene, ARID1B. This variant was absent in peripheral blood samples obtained from both parents and unaffected siblings. Therefore, we propose that the most likely explanation for this situation is that one of the parents is a gonadal mosaic for the variant. To the best of our knowledge, this is the first report of a gonadal mosaicism inheritance of an ARID1B variant leading to familial ID recurrence. © 2015 Wiley Periodicals, Inc.

‘And Then He Switched off the Phone’: Mobile Phones, Participation and Political Accountability in South Sudan’s Western Equatoria State

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Mareike Schomerus

2015-03-01

Full Text Available This paper uses qualitative and quantitative original data to investigate the impact of mobile phones in situations of political contestation or conflict. We derive hypotheses from theories in general political science, and on the role of mobile phones specifically. These suggest that a link exists between access to better communication structures, political participation and government accountability. Given such a link, information and communications technologies—specifically mobile phones—could play a positive role in building a more accountable government, and with that, contribute to statebuilding. We examine to what extent these hypotheses hold true for ordinary citizens in South Sudan's Western Equatoria State (WES. Using interdisciplinary methods, we use data gathered through in-depth interviews and a quantitative survey and find little evidence that mobile phone coverage contributes to statebuilding or peacebuilding through a causal link between information, voting, political participation and government accountability. In a situation where administrative structures and mechanisms do not exist for citizens to hold politicians accountable, access to mobile phones might mean greater dissatisfaction with political participation and voting. People living in areas without coverage expressed a deep mistrust of government, and appeared to want to withdraw from the system of government entirely.

Waste incineration. Final report

Energy Technology Data Exchange (ETDEWEB)

Egede Rasmussen, Anja

2004-06-15

This prepatory thesis is a literature study on the incineration of waste. It deals with the concepts of municipal solid waste, the composition and combustion of it. A main focus is on the European emission regulations and the formation of dioxins, as well as a big effort is put into the treatment of solid residues from municipal solid waste incineration. In the latter area, concepts of treatment, such as physical and chemical separations, solidification and stabilization techniques, thermal methods, and extraction methods have been discussed. Evaluation of possible methods of treatment has been done, but no conclusions made of which is the best. Though, indications exist that especially two methods have shown positive qualities and must be further investigated. These methods are the acid extraction and sulfide stabilization (AES) process and the phosphate stabilization method of WES-PHix. Economic potentials of the two methods have been evaluated, and with the information obtained, it seems that the price for treatment and later landfilling of a material with improved leaching characteristics, will be approximately the same as the presently most used solution of export to Norway. However, more tests, investigations and economic evaluations are necessary in order for support of the findings in this work. (au)

Rhetoric Tradition and Democracy: Isocrates’ Role in Ancient Greek Political Idea. Start Point of Western Political Philosophy

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Shokri Mehdi

2015-07-01

Full Text Available Political participation and the public education that have always been deployed to support the incipient progress of the civic life are revived in the modern political discourses. It has been believed that the age of pre-Socrates was the age of the Sophists whose acrid fallacy works occupied the political sphere, a malaise in government. However, speaking non-traditionally in the modern pedagogical system, there were some pre-Socratic thinkers and political philosophers/orators who’s works are the backbone of modern discourse on this matter. It will be examined whether any part of the classical rhetoric apparatus can be recovered and put to a good practice in the modern education and modern political participation. This point will be illustrated, furthermore, in this paper by alleging the importance of rhetoric, its role in Ancient Greek Democracy, and its influence on the modern concepts of power and democracy, as a continual element in a historical-political life. The further consideration is whether there was any democratic Polis existed in Ancient Athens and then, if there was, what characteristics it consisted of. Moreover, whether such concept can or should be considered in modern political discourses. In this sense, the liberal, non-dogmatic strain of the sophistry of Isocrates tradition urges us to indicate that the findings of this educational principles are, if not necessary, but adjutant complementary metes to our modern political knowledge of the states. In the end, it is inquired to see comparatively that how the tradition of rhetorical art and the concept of power in the Ancient Greek society have pertained to the modern democratic elements and whether we are able to empower this influential element in modern states.