Unpacking the Millennials: A Cautionary Tale for Teacher Education

ERIC Educational Resources Information Center

Donnison, Sharn

2007-01-01

This paper is about the millennial generation. Much has been written about the generation: their character; beliefs; motivations; values; and future potentialities. This literature has gained momentum as marketers, employers, and educators seek to understand the generation as they come of age and enter into positions of social responsibility. The…

Nontraditional Students, Accelerated Programs, Grade Expectations, and Instructor Evaluations

ERIC Educational Resources Information Center

Gershuny, Pamela; Rainey, Carolyn

2006-01-01

This article is intended as both a cautionary tale and an encouraging guide for instructors who are beginning to teach in accelerated programs designed to attract nontraditional students. This article is based, in part, on classroom action research conducted through surveys, observations, exams, and assessments, in an introductory business law…

Athletics and Academic Achievement in Latino Youth: A Cautionary Tale

ERIC Educational Resources Information Center

Chen, Wei; Harklau, Linda

2017-01-01

Participation in extracurricular activities has been associated with enhanced academic achievement in Latino youth. Based on a longitudinal case study of one immigrant adolescent, this article finds that athletic participation is in itself neither a wholly positive or negative influence on Latino school achievement. Rather, effects of…

As Budgets Swell, Spending Choices Get New Scrutiny

ERIC Educational Resources Information Center

McNeil, Michele

2007-01-01

When lawmakers in Arkansas increased school funding by more than $700 million over the past three years to improve student achievement, they wanted the money to be spent on instructional coaches for teachers, tutors for struggling students, and smaller class sizes in reading, math, and science. However--in what could prove a cautionary tale for…

Data Mine and Forget It?: A Cautionary Tale

NASA Technical Reports Server (NTRS)

Tada, Yuri; Kraft, Norbert Otto; Orasanu, Judith M.

2011-01-01

With the development of new technologies, data mining has become increasingly popular. However, caution should be exercised in choosing the variables to include in data mining. A series of regression trees was created to demonstrate the change in the selection by the program of significant predictors based on the nature of variables.

Dancing with History: A Cautionary Tale

ERIC Educational Resources Information Center

Gourley, Brenda

2010-01-01

Lessons from history lead to questions for the future of higher education: is innovation being embraced quickly enough, have universities reached a scale necessary to the task, can technology help, can higher education institutions bring more hands to the wheel, and are they managing and leading in appropriate ways? Trends in higher education play…

Linking Grades and College Graduates' Perceptions of Obstacles and Facilitators: A Cautionary Tale

ERIC Educational Resources Information Center

Jorgensen, Shirley; Fichten, Catherine S.

2007-01-01

We set out to compare the relationship between the standardized grade averages (CRC scores) of recent college graduates with and without disabilities at a large English CEGEP [College of General and Professional Education]. We also examined the relationship between graduates' perceptions of facilitators and obstacles to academic success, and their…

Cautionary Tales on Interrupting Children's Play: A Study from Sweden

ERIC Educational Resources Information Center

Weldemariam, Kassahun Tigistu

2014-01-01

Play is a natural and significant aspect of children's learning and development. Adults can be important to children's play, as they act as "play agents." Their involvement significantly influences the quality of the play activities in which children engage. The author briefly reviews the theoretical assumptions about adults' role in…

The Unexamined Relationship between Neoliberalism and Plurilingualism: A Cautionary Tale

ERIC Educational Resources Information Center

Flores, Nelson

2013-01-01

In recent years, TESOL scholars have offered both explicit and implicit critiques of language ideologies developed within nationalist frameworks that positioned monolingualism in a standardized national language as the desired outcome for all citizens. These scholars have used insights from both the social and the natural sciences to call into…

Seeing Like PISA: A Cautionary Tale about the Performativity of International Assessments

ERIC Educational Resources Information Center

Gorur, Radhika

2016-01-01

PISA is an extremely influential large-scale assessment, and its "policy lessons" are being incorporated in a range of nations all over the world. In this paper I argue that not only is PISA influencing policies and practices, but also that "seeing like PISA" is becoming a widespread phenomenon. Globally, education…

Litigating Grades: A Cautionary Tale

ERIC Educational Resources Information Center

Lewis, Lionel S.

2005-01-01

This account of an academic lawsuit qualifies as a horror story. A mediocre minority student abuses civil rights and ADA protections to win a massive monetary award against his school on the flimsiest of evidence. Jaded lawyers for the state university represent powerless faculty defendants in court, torpidly allowing the jury to throw 50 years of…

Deconstructing Discourses about "New 'Paradigms' of Teaching": A Foucaultian and Wittgensteinian Perspective

ERIC Educational Resources Information Center

Stickney, Jeff

2006-01-01

Offering a cautionary tale about the abuses of paradigm-shift rhetoric in secondary school reforms, the paper shows potential misuses and ethical effects of the relativistic language-game in post-compulsory education. Those initiating the shift often shelter their reform from the criticism of non-adepts, marginalizing expert teachers that adhere…

Operation Cottage: A Cautionary Tale of Assumption and Perceptual Bias

DTIC Science & Technology

2015-01-01

dealing with churning seas and 25-degree tem- peratures, but it did not bode well for an advance to the island interior, which now faced murderous mortar...but this scheme was aborted in late June after three submarines as- signed to the operation were detected and sunk by Allied destroyers.39 It was

Virtual Reference Services--Down-Under: A Cautionary Tale.

ERIC Educational Resources Information Center

Wagner, Gulten S.

Digital reference services at university libraries in Australia and New Zealand are a recent phenomena dating back to the late 1990s--following the developments in Web-based online library services. This paper examines the move towards the provision of e-mail reference services based on the study of 16 randomly chosen university libraries in…

Safe at Home

ERIC Educational Resources Information Center

O'Hanlon, Charlene

2009-01-01

Since laptop programs extend instruction beyond the campus, it is then a must for schools to try a variety of solutions to protect their machines--and their users. Combining high-tech safeguards with face-to-face user education is a must for schools whose laptop programs allow students to take the computers off-site. For a cautionary tale on the…

Computer-Mediated Communication and a Cautionary Tale of Two Cities

ERIC Educational Resources Information Center

Sadler, Randall

2007-01-01

This paper describes an action research project that investigated the pedagogical applicability of computer-mediated communication (CMC) tools for collaborative projects. The research involved two groups of students studying to become ESL/EFL teachers, one group at a university located in the US Midwest and the other in the Catalan region of…

Accreditation in the Profession of Psychology: A Cautionary Tale

ERIC Educational Resources Information Center

Maiden, Robert; Knight, Bob G.; Howe, Judith L.; Kim, Seungyoun

2012-01-01

This article examines the history of accreditation in psychology and applies the lessons learned to the Association for Gerontology in Higher Education's (AGHE) consideration of forming an organization to accredit programs in gerontology. The authors identify the challenges met and unmet, the successes and failures, and the key issues that emerged…

Electronic Portfolios in Grades One, Two and Three: A Cautionary Tale

ERIC Educational Resources Information Center

Kotsopoulos, Donna; Lee, Joanne; Cordy, Michelle; Bruyns, Susan

2015-01-01

Some electronic portfolios (EPs) developers are proposing that EPs are suitable for implementation in primary education (i.e. kindergarten to grade three). Yet, empirical research evaluating the implementation and efficacy of EPs used in primary school settings at both the teacher and the student level is scarce. In this research, the authors…

School-University Partnerships and Teacher Leadership: Doing It Right

ERIC Educational Resources Information Center

Miller, Lynne

2015-01-01

Drawing on the author's experience as director of a long-lived school-university partnership, this essay describes how one such organization can "do it right" and enhance the development of teacher leadership in schools. It also provides a cautionary tale about how that same organization can "do it wrong" and achieve the…

Evidence, Policy and the Reform of Primary Education: A Cautionary Tale

ERIC Educational Resources Information Center

Alexander, Robin

2014-01-01

Here, at "FORUM's" invitation, is the text of the 2014 Godfrey Thomson Trust public lecture at the University of Edinburgh. Its backdrop is the centralisation of educational decision-making in England since 1988 and the power and patronage exercised by the Secretary of State. Taking as examples recent policies on childhood, curriculum…

Things (We Now Believe) We Know

ERIC Educational Resources Information Center

Skidmore, Susan Troncoso; Thompson, Bruce

2012-01-01

The present article responds briefly to the comments, in this issue of "Educational Researcher," of Petrosino and of Robinson to the "Propagation of Misinformation About Frequencies of RFTs/RCTs in Education: A Cautionary Tale." The authors emphasize that the context of how the quality of education research is perceived both within and outside the…

Online Methods and Analyzing Knowledge-Production: A Cautionary Tale

ERIC Educational Resources Information Center

Ignacio, Emily Noelle

2012-01-01

Currently, many scholars have increasingly turned to the Internet to examine diasporic communities and corresponding identities. While I am happy that social scientists have embraced the use of online methods in studying communities formed within cyberspace, I also believe that we should continually reflect on whether our research is best served…

Teaching the Holocaust as a Cautionary Tale

ERIC Educational Resources Information Center

Marks, Melissa J.

2017-01-01

Teaching about the Holocaust as an atrocity of the 1940s misleads students into thinking that it is a genocide occurred, that the world agreed "Never Again," and that the United Nations would prevent future genocides. With genocides in Rwanda, Srebrenica, and Syria occurring in the years since the Holocaust, teachers need to use the…

Teaching Practical Science Online Using GIS: A Cautionary Tale of Coping Strategies

ERIC Educational Resources Information Center

Argles, Tom

2017-01-01

Strong demand for GIS and burgeoning cohorts have encouraged the delivery of GIS teaching via online distance education models. This contribution reviews a brief foray (2012-2014) into this field by the Open University, deploying open source GIS software to enable students to perform practical science investigations online. The "Remote…

Cautionary Tales

ERIC Educational Resources Information Center

Stuart, Reginald

2010-01-01

When Kemba Smith Pradia spoke this fall to a gathering of students at South Carolina State University, her candid talk about violence against women and the campus "hype" over drugs, sex, and money resonated with students and faculty alike. Ten years ago, Kemba Smith was wasting away in a federal prison as prisoner No. 26370-083. Used by…

Child Soldiers and Iconography: Portrayals and (Mis)Representations

ERIC Educational Resources Information Center

Denov, Myriam

2012-01-01

Over the past decade, child soldiers have inundated the popular media. Images of boys armed with AK47s appear ubiquitous, providing a cautionary tale of innocent childhood gone awry. While these representations turn commonly held assumptions of a protected and innocuous childhood on its head, what they conceal is as provocative as what they…

Teacher Effects on Student Achievement and Height: A Cautionary Tale

ERIC Educational Resources Information Center

Bitler, Marianne P.; Corcoran, Sean P.; Domina, Thurston; Penner, Emily K.

2014-01-01

The growing availability of data linking students to classroom teachers has made it possible to estimate the contribution teachers make to student achievement. While there is a growing consensus that teacher quality is important and current evaluation systems are inadequate, many have expressed concerns over the use of value-added measures (VAMs)…

Updating a Cautionary Tale of Masked Priming: Reply to Klapp (2005)

ERIC Educational Resources Information Center

Lleras, Alejandro; Enns, James T.

2005-01-01

The commentary by S. T. Klapp (see record 2005-09704-010) on our recent article (A. Lleras & J. T. Enns, [see record 2004-21166-001]) proposes that the empirical finding of negative compatibility in masked priming be attributed to 2 distinct theoretical constructs: (a) perceptual priming through object updating, as described in our article, and…

Rationality as Rhetorical Strategy at the Barcelona Disputation, 1263: A Cautionary Tale

ERIC Educational Resources Information Center

Bizzell, Patricia

2006-01-01

Often, composition teachers present public debate as if it occurs on a rhetorically level playing field, with victory going to the person who argues most logically. Real-world contestants are seldom so equal in power. We can enrich our pedagogy by studying such encounters; example: the 1263 disputation at Barcelona between Rabbi Nachmanides and…

Talking up Learning at Work: Cautionary Tales in Co-Opting Everyday Learning

ERIC Educational Resources Information Center

Boud, David; Rooney, Donna; Solomon, Nicky

2009-01-01

Learning in workplaces is always mediated through talk. It is tempting for management to seek to utilise everyday talk as part of learning and therefore enhance productivity. This paper examines the responses of workers to interventions that aim to formalise informal conversations at work as part of an explicit workplace learning strategy. It…

A Longitudinal Study of Teaching Practice and Early Career Decisions: A Cautionary Tale

ERIC Educational Resources Information Center

Cochran-Smith, Marilyn; McQuillan, Patrick; Mitchell, Kara; Terrell, Dianna Gahlsdorf; Barnatt, Joan; D'Souza, Lisa; Jong, Cindy; Shakman, Karen; Lam, Karen; Gleeson, Ann Marie

2012-01-01

Although the turnover rate among beginning teachers has been a major concern for some time, most studies do not link teacher retention with teaching practice. In contrast, this study looks specifically at career decisions coupled with practice. Guided by a view of teaching as social and cultural practice, the study used multiple qualitative data…

A Case Study of District Decentralization and Site-Based Budgeting: Cordell Place School District.

ERIC Educational Resources Information Center

Fermanich, Mark; Odden, Allan; Archibald, Sarah

A previously high-ranking suburban school district with declining student achievement changed to site-based budgeting. The account of the change may also be a cautionary tale about change taken too rapidly. Although a poor economy, the annexation of two Department of Defense schools, and organizational stagnation helped to create lower student…

ESL Teacher Education Abroad and at Home: A Cautionary Tale

ERIC Educational Resources Information Center

Pray, Lisa; Marx, Sherry

2010-01-01

In this article, we compared teacher attitudes and beliefs about culturally appropriate language teaching resulting from an examination of two groups of preservice teachers. One group of preservice teachers enrolled in an English as a Second Language (ESL) study abroad program in Mexico; the other enrolled in a traditional on-campus ESL program.…

Cautionary Tales: Strategy Lessons from Struggling Colleges

ERIC Educational Resources Information Center

Brown, Alice W.

2012-01-01

Scarcely a week goes by without a headline about the unsustainability of higher education as we know it, under threat from new models, for-profits, or online education. Most threatened are small liberal arts colleges--with commentators predicting the demise of colleges with fewer than 1,000, or even 1,500 students. Are these trends inevitable, or…

Pursuing Tenure and Promotion in the Academy: A Librarian's Cautionary Tale

ERIC Educational Resources Information Center

Griffin, Karin L.

2013-01-01

The author examines her journey before and as she pursued tenure and promotion in the academy. She argues that the path to tenure and promotion in higher education institutions was not one designed to provide a fair and equitable process for Black female faculty who function as academic librarians. Further, she suggests that librarians in this…

On the blind use of statistical tools in the analysis of globular cluster stars

NASA Astrophysics Data System (ADS)

D'Antona, Francesca; Caloi, Vittoria; Tailo, Marco

2018-04-01

As with most data analysis methods, the Bayesian method must be handled with care. We show that its application to determine stellar evolution parameters within globular clusters can lead to paradoxical results if used without the necessary precautions. This is a cautionary tale on the use of statistical tools for big data analysis.

Book review of "The estrogen elixir: A history of hormone replacement therapy in America" by Elizabeth Siegel Watkins

PubMed Central

Sonnenschein, Carlos

2008-01-01

"The Estrogen elixir: A history of hormone replacement therapy in America" by Elizabeth Siegel Watkins is a thoroughly documented cautionary tale of the information and advice offered to women in the perimenopausal period of their life, and the consequences of exposure to sexual hormones on their health and wellbeing.

Career Guidance and Social Exclusion: A Cautionary Tale.

ERIC Educational Resources Information Center

Watts, A. G.

2001-01-01

Examines the relationship of career guidance to public-policy interventions designed to address social exclusion. Analyzes the nature and origin of the concept of social exclusion and reviews the roles of career guidance in response to it, particularly in relation to young people who have dropped out of formal education or are at high risk of…

A Preliminary Methodology, and a Cautionary Tale, for Determining How Students Seek Research Help Online

ERIC Educational Resources Information Center

Pellegrino, Catherine

2014-01-01

This article reports on a pilot study to examine undergraduate students' help-seeking behavior when undertaking library research in online courses. A novel methodology incorporating elements of ethnographic research resulted in a small, but rich and detailed, collection of qualitative data. The data suggest that the methodology has promise for…

Smart Boys: Talent, Manhood, and the Search for Meaning.

ERIC Educational Resources Information Center

Kerr, Barbara A.; Cohn, Sanford J.

This book explores issues faced by gifted boys and men and the concerns of those around them. Section 1, "Giftedness and Masculinity," explores the relationship of special intellectual ability to the role of males in our society. The findings of a study on the male graduates of the accelerated learning class of 1969 are used as a cautionary tale.…

The Rise and Fall of Supplemental Educational Services: Policy Implications for Government Markets

ERIC Educational Resources Information Center

Mesecar, Doug

2015-01-01

Free after-school tutoring, known as supplemental educational services (SES), was brought to life by the No Child Left Behind Act (NCLB) in 2002. SES was designed to provide extra academic assistance to low-income students in schools failing to make accountability targets. SES is a cautionary tale, for there has never been an experiment like it in…

Reinventing First-Year Composition at the First Land-Grant University: A Cautionary Tale.

ERIC Educational Resources Information Center

Graham, Margaret Baker; Birmingham, Elizabeth; Zachry, Mark

1997-01-01

Examines the restructuring of first-year composition at Iowa State University. Discusses the exodus of tenure-track faculty from first-year composition in the late 1970's and early 1980's; why upper administration is now mandating tenure-track faculty's return; why the department of English is cooperating; and potential risks in cooperating or not…

Reforming the School Curriculum and Assessment in England to Match the Best in the World--A Cautionary Tale

ERIC Educational Resources Information Center

Steers, John

2014-01-01

This article traces the development of a new National Curriculum in England following the general election of 2010. The prevailing political ideology of an approach based on securing "core knowledge" in a limited range of preferred "academic" subjects and its deleterious impact on the arts in schools is described. The vigorous…

Collegiate Connections: The Story of a Licensed Teacher in a Paraprofessional Music Position--A Cautionary Tale

ERIC Educational Resources Information Center

Conway, Colleen; Rawlings, Jared; Wolfgram, T. J.

2014-01-01

A trained music educator accepted a band paraprofessional position and discovered some of the challenges inherent in the role. Certified for K-12 music, he was hired part-time in a large suburban instrumental music program. The job, although interesting and challenging, did not pay enough to sustain him financially. Other music educators warned…

"I Think It's Low Self-Esteem". Teachers' Judgements: A Cautionary Tale

ERIC Educational Resources Information Center

Miller, David; Parker, Donna

2006-01-01

Although there is a debate about the importance of self-esteem in education, many primary teachers wish to help children who suffer from low self-esteem. However, in order to do this, we first have to identify such children. It is almost taken for granted that we can make quite accurate judgements based on the knowledge built up through day-to-day…

Exploring the Underlying Factor Structure of the Home Literacy Environment (HLE) in the English and Spanish Versions of the Familia Inventory: A Cautionary Tale

ERIC Educational Resources Information Center

Gonzalez, Jorge E.; Taylor, Aaron B.; McCormick, Anita S.; Villareal, Victor; Kim, Minjung; Perez, Erica; Darensbourg, Alicia; Haynes, Rebekah

2011-01-01

Few research-based measures of the family literacy environment are commercially available, especially in Spanish. One exception is the Familia Inventory (Taylor, 1995). The present study investigated the 10 subscales of this instrument and the factor structure they imply, using data from a low-socioeconomic (SES), largely Hispanic population.…

An Examination of the Dirty Dozen Measure of Psychopathy: A Cautionary Tale about the Costs of Brief Measures

ERIC Educational Resources Information Center

Miller, Joshua D.; Few, Lauren R.; Seibert, L. Alana; Watts, Ashley; Zeichner, Amos; Lynam, Donald R.

2012-01-01

Given substantial interest in the traits conceived of as part of the "Dark Triad"--psychopathy, narcissism, and Machiavellianism--assessment of these traits is of great importance. The Dirty Dozen (DD; Jonason & Webster, 2010) is a brief measure of the Dark Triad constructs that uses 4 items to assess each of these constructs. In the present…

Modeling loblolly pine aboveground live biomass in a mature pine-hardwood stand: a cautionary tale

Treesearch

D. C. Bragg

2011-01-01

Carbon sequestration in forests is a growing area of interest for researchers and land managers. Calculating the quantity of carbon stored in forest biomass seems to be a straightforward task, but it is highly dependent on the function(s) used to construct the stand. For instance, there are a number of possible equations to predict aboveground live biomass for loblolly...

The Hippocratic Need for Adequate Supports While Merging Programs: At First Do No Harm

ERIC Educational Resources Information Center

Sipple, John W.

2017-01-01

In response to a paper calling for the re-engagement of agricultural education with the sciences and science education, this essay is supportive but argues to proceed with caution: one that at first does no harm. I offer a supplementary lens and story of change at Cornell University as a cautionary and motivational tale. I concur with the authors…

Cautionary Tales: Ethics and Case Studies in Science

PubMed Central

Herreid, Clyde Freeman

2014-01-01

Ethical concerns are normally avoided in science classrooms in spite of the fact that many of our discoveries impinge directly on personal and societal values. We should not leave the ethical problems for another day, but deal with them using realistic case studies that challenge students at their ethical core. In this article we illustrate how case studies can be used to teach STEM students principles of ethics. PMID:25574280

Crisis and Escalation in Cyberspace

DTIC Science & Technology

2012-01-01

state’s ability to censor the Internet within its own boundaries, for instance, would not be well received in the United States. 39 CHAPTER THREE...producers elsewhere in Asia and Latin America . China’s physical investments in the West, although growing, are far smaller than the West’s invest...ensure that they always are available. On a somewhat different note, the 1983 movie War Games, besides offering a cautionary tale against nuclear war in

Bantam: A Cautionary Tale

NASA Technical Reports Server (NTRS)

McNeal, Curtis I., Jr.

2004-01-01

This viewgraph presentation reviews the history of the Bantam program that was cancelled in 1999 due to the decision that the focus on the small payloads was unsustainable and that there would be no return on investment. The comparison is made between NASA's Bantam program, and DARPA's (Defense Advanced Research Projects Agency) two similar projects (Falcon and Rascal). The Bantam Program was to be a small launch vehicle, aimed at launching small payloads (i.e., of 150-300 kg) into space.

Government public health policy: three cautionary tales from Malaysia, South Africa and the United States.

PubMed

Blum, John; Carstens, Pieter; Talib, Norchaya

2007-12-01

Three authors describe problematic scenarios of health policy in their respective countries. These examples illustrate the role of government influences in determining resource allocation, legislation, health provision and health outcomes in very different situations. These outcomes are affected not only by attitudes to public health, but also by the legal systems in the countries which are the subjects of this study. The authors draw conclusions about the use and abuse of public health regulation.

Cautionary tales for reduced-gravity particle research

NASA Technical Reports Server (NTRS)

Marshall, John R.; Greeley, Ronald; Tucker, D. W.

1987-01-01

Failure of experiments conducted on the KC-135 aircraft in zero gravity are discussed. Tests that were a total failure are reported. Why the failure occurred and the sort of questions that potential researchers should ask in order to avoid the appearance of abstracts such as this are discussed. Many types of aggregation studies were proposed for the Space Station, and it is hoped that the following synopsis of events will add a touch of reality to experimentation proposed for this zero-gravity environment.

Rapid reduction of antihypertensive medications and insulin requirements after tracheostomy in a patient with severe obstructive sleep apnea syndrome.

PubMed

Bhimaraj, Arvind; Havaligi, Navasuma; Ramachandran, Siva

2007-04-15

We report a patient with severe obstructive sleep apnea syndrome, diabetes mellitus, and hypertension, with postoperative complications following tracheostomy. His stormy postoperative course is presented with emphasis on glycemic control and hypertension. We present a cautionary tale of a significant reduction in medications to control blood pressure and hyperglycemia following tracheostomy for severe OSA. The severe reduction in blood pressure and hypoglycemia could mimic sepsis and clinicans need to be vigilant to these dramatic effects following tracheostomy and appropriately adjust baseline medications.

Absolute spectrophotometry of Wolf-Rayet stars from 1200 to 7000 A - A cautionary tale

NASA Technical Reports Server (NTRS)

Garmany, C. D.; Conti, P. S.; Massey, P.

1984-01-01

It is demonstrated that absolute spectrophotometry of the continua of Wolf-Rayet stars may be obtained over the wavelength range 1200-7000 A using IUE and optical measurements. It is shown that the application of a 'standard' reddening law to the observed data gives spurious results in many cases. Additional UV extinction is apparently necessary and may well be circumstellar in origin. In such hot stars, the long-wavelength 'tail' of the emergent stellar continuum are measured. The inadequacy of previous attempts to determine intrinsic continua and effective temperatures of Wolf-Rayet stars is pointed out.

Resident Work Hour Restrictions and Change Management: A Cautionary Tale.

PubMed

Fang, Z Amy; Hudson, Darren

2015-01-01

Residents are a significant part of coverage in many hospitals. Resident associations are negotiating work hour limits to prevent fatigue-induced medical errors. Our intensive care unit experienced an unexpected resident shortage and used the opportunity to trial a shift schedule for one month. Post-surveys were sent to nurses, attending physicians and residents to evaluate the effects on staff interactions, patient safety and education quality. The trial was clearly a failure on all fronts. Work hour restrictions are a reality in medical education, and administrators need to start considering alternative staffing models and discussing alternative schedules with their medicine faculty.

Anatomising proton NMR spectra with pure shift 2D J-spectroscopy: A cautionary tale

NASA Astrophysics Data System (ADS)

Kiraly, Peter; Foroozandeh, Mohammadali; Nilsson, Mathias; Morris, Gareth A.

2017-09-01

Analysis of proton NMR spectra has been a key tool in structure determination for over 60 years. A classic tool is 2D J-spectroscopy, but common problems are the difficulty of obtaining the absorption mode lineshapes needed for accurate results, and the need for a 45° shear of the final 2D spectrum. A novel 2D NMR method is reported here that allows straightforward determination of homonuclear couplings, using a modified version of the PSYCHE method to suppress couplings in the direct dimension. The method illustrates the need for care when combining pure shift data acquisition with multiple pulse methods.

Are Wearables Safe? We Carry Our Smart Devices with Us Everywhere--Even to Bed--But Have We Been Sleeping with the Enemy, or are Cautionary Tales Overinflated?

PubMed

Mertz, Leslie

2016-01-01

Sometime over the last few years, wearable electronics have become the norm. Whether it's a cell phone attached to a holster at the hip, a smart watch on the wrist, or sensors on and sometimes woven into clothing, these technologies are part of everyday life. Along with this trend, many of the devices are also now collecting and transmitting health information. That is certainly convenient, but the question with any kind of health care device, including wearable medical technology, has always been and continues to be: is it safe?

Robert Waelder and the application of psychoanalytic principles to social and political phenomena.

PubMed

Guttman, S A

1986-01-01

This presentation reveals a little-known area of Robert Waelder's work. As his literary executor, I have been privileged with access to his unpublished material, notes, and correspondence. And, of course, I am familiar with his mode of thinking. I wish to pass on some of this knowledge. What cannot be passed on, however, in some abstract intellectual way, are psychoanalytic principles themselves. Therefore, while this paper sheds light on a very particular aspect of Robert Waelder's work, it is also in some ways a cautionary tale, a plea that the reader understand what is behind the psychoanalytic point of view and its basic concepts--namely, clinical experience.

Medicare Readmissions Policies and Racial and Ethnic Health Disparities: A Cautionary Tale

PubMed Central

McHugh, Matthew D.; Carthon, J. Margo Brooks; Kang, Xiao L.

2011-01-01

Beginning in 2009, the Centers for Medicare & Medicaid Services started publicly reporting hospital readmission rates as part of the Hospital Compare website. Hospitals will begin having payments reduced if their readmission rates are higher than expected starting in fiscal year 2013. Value-based purchasing initiatives including public reporting and pay-for-performance incentives have the potential to increase quality of care. There is concern, however, that hospitals providing service to minority communities may be disproportionately penalized as a result of these policies due to higher rates of readmissions among racial and ethnic minority groups. Using 2008 Medicare data, we assess the risk for readmission for minorities and discuss implications for minority-serving institutions. PMID:21531966

Unexpected findings and promoting monocausal claims, a cautionary tale.

PubMed

Copeland, Samantha Marie

2017-10-01

Stories of serendipitous discoveries in medicine incorrectly imply that the path from an unexpected observation to major discovery is straightforward or guaranteed. In this paper, I examine a case from the field of research about chronic fatigue syndrome (CFS). In Norway, an unexpected positive result during clinical care has led to the development of a research programme into the potential for the immunosuppressant drug rituximab to relieve the symptoms of CFS. The media and public have taken up researchers' speculations that their research results indicate a causal mechanism for CFS - consequently, patients now have great hope that 'the cause' of CFS has been found, and thus, a cure is sure to follow. I argue that a monocausal claim cannot be correctly asserted, either on the basis of the single case of an unexpected, although positive, result or on the basis of the empirical research that has followed up on that result. Further, assertion and promotion of this claim will have specific harmful effects: it threatens to inappropriately narrow the scope of research on CFS, might misdirect research altogether, and could directly and indirectly harm patients. Therefore, the CFS case presents a cautionary tale, illustrating the risks involved in drawing a theoretical hypothesis from an unexpected observation. Further, I draw attention to the tendency in contemporary clinical research with CFS to promote new research directions on the basis of reductive causal models of that syndrome. Particularly, in the case of CFS research, underdetermination and causal complexity undermine the potential value of a monocausal claim. In sum, when an unexpected finding occurs in clinical practice or medical research, the value of following up on that finding is to be found not in the projected value of a singular causal relationship inferred from the finding but rather in the process of research that follows. © 2016 John Wiley & Sons, Ltd.

Comparative analysis of human ex vivo–generated platelets vs megakaryocyte-generated platelets in mice: a cautionary tale

PubMed Central

Wang, Yuhuan; Hayes, Vincent; Jarocha, Danuta; Sim, Xiuli; Harper, Dawn C.; Fuentes, Rudy; Sullivan, Spencer K.; Gadue, Paul; Chou, Stella T.; Torok-Storb, Beverly J.; Marks, Michael S.; French, Deborah L.

2015-01-01

Thrombopoiesis is the process by which megakaryocytes release platelets that circulate as uniform small, disc-shaped anucleate cytoplasmic fragments with critical roles in hemostasis and related biology. The exact mechanism of thrombopoiesis and the maturation pathways of platelets released into the circulation remain incompletely understood. We showed that ex vivo–generated murine megakaryocytes infused into mice release platelets within the pulmonary vasculature. Here we now show that infused human megakaryocytes also release platelets within the lungs of recipient mice. In addition, we observed a population of platelet-like particles (PLPs) in the infusate, which include platelets released during ex vivo growth conditions. By comparing these 2 platelet populations to human donor platelets, we found marked differences: platelets derived from infused megakaryocytes closely resembled infused donor platelets in morphology, size, and function. On the other hand, the PLP was a mixture of nonplatelet cellular fragments and nonuniform-sized, preactivated platelets mostly lacking surface CD42b that were rapidly cleared by macrophages. These data raise a cautionary note for the clinical use of human platelets released under standard ex vivo conditions. In contrast, human platelets released by intrapulmonary-entrapped megakaryocytes appear more physiologic in nature and nearly comparable to donor platelets for clinical application. PMID:25852052

Time-Series Analysis: A Cautionary Tale

NASA Technical Reports Server (NTRS)

Damadeo, Robert

2015-01-01

Time-series analysis has often been a useful tool in atmospheric science for deriving long-term trends in various atmospherically important parameters (e.g., temperature or the concentration of trace gas species). In particular, time-series analysis has been repeatedly applied to satellite datasets in order to derive the long-term trends in stratospheric ozone, which is a critical atmospheric constituent. However, many of the potential pitfalls relating to the non-uniform sampling of the datasets were often ignored and the results presented by the scientific community have been unknowingly biased. A newly developed and more robust application of this technique is applied to the Stratospheric Aerosol and Gas Experiment (SAGE) II version 7.0 ozone dataset and the previous biases and newly derived trends are presented.

Enterobius vermicularis (pinworm) infestation in a child presenting with symptoms of acute appendicitis: a wriggly tale!

PubMed

Dunphy, Louise; Clark, Zoe; Raja, Mazhar H

2017-10-06

Acute appendicitis is the most common surgical emergency worldwide. However, it can still present a challenging diagnosis especially in the young, elderly and those individuals of reproductive age, thus encompassing a wide spectrum of varied clinical presentations. Parasitic infections of the appendix are a rare cause of acute appendicitis. However, they must be considered in children presenting with abdominal pain. We report a case of Enterobius vermicularis infestation mimicking the features of acute appendicitis in a 10-year-old girl. This case is a cautionary reminder of the importance of considering E. vermicularis infestation in children presenting with abdominal pain, but who do not have a significantly raised white cell count or high Alvarado scores. A history of anal pruritus is the most characteristic symptom, but the parasites can cause severe abdominal pain mimicking appendicitis. Prompt recognition and a high clinical index of suspicion are required to prevent an unnecessary appendicectomy. Caution is advised when performing a laparoscopic appendectomy, as in our case, to prevent contamination of the peritoneum. This infestation is easily treatable with mebendazole. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The effect of stellar-mass black holes on the central kinematics of ω Cen: a cautionary tale for IMBH interpretations

NASA Astrophysics Data System (ADS)

Zocchi, Alice; Gieles, Mark; Hénault-Brunet, Vincent

2018-06-01

The search for intermediate-mass black holes (IMBHs) in the centre of globular clusters is often based on the observation of a central cusp in the surface brightness profile and a rise towards the centre in the velocity dispersion profiles. Similar signatures, however, could result from other effects, that need to be taken into account in order to determine the presence (or the absence) of an IMBH in these stellar systems. Following our previous exploration of the role of radial anisotropy in shaping these observational signatures, we analyse here the effects produced by the presence of a population of centrally concentrated stellar-mass black holes. We fit dynamical models to ω Cen data, and we show that models with ˜5% of their mass in black holes (consistent with ˜100% retention fraction after natal kicks) can reproduce the data. When simultaneously considering both radial anisotropy and mass segregation, the best-fit model includes a smaller population of remnants, and a less extreme degree of anisotropy with respect to the models that include only one of these features. These results underline that before conclusions about putative IMBHs can be made, the effects of stellar-mass black holes and radial anisotropy need to be properly accounted for.

A cautionary tale: The Coulomb modified ANC for the 1/2+ 2 state in 17O

NASA Astrophysics Data System (ADS)

Keeley, N.; Kemper, K. W.; Rusek, K.

2018-05-01

We discuss the impact of the uncertainty (± 8 keV) in the excitation energy of the astrophysically important 6.356 MeV 1/2+2 state of 17O on the precision with which the Coulomb reduced ANC (\\widetilde{C}) for the < ^{17}O (1/2^+_2) | {}^{13}C + α> overlap can be extracted from direct reaction data. We find a linear dependence of \\widetilde{C}2 on the binding energy, the value extracted varying by a factor of 4 over the range E_{ex} = 6.356-6.348 MeV. This represents an intrinsic limit on the precision with which \\widetilde{C}2 can be determined which cannot be improved unless or until the uncertainty in E_{ex} is reduced.

Cautionary tales in the interpretation of observational studies of effects of clinical interventions.

PubMed

Scott, I A; Attia, J

2017-02-01

Observational studies of the effectiveness of clinical interventions are proliferating as more 'real-world' clinical data (so called 'big data') are gathered from clinical registries, administrative datasets and electronic health records. While well-conducted randomised controlled trials (RCT) remain the scientific standard in assessing the efficacy of clinical interventions, well-designed observational studies may add to the evidence base of effectiveness in situations where RCT are of limited value or very difficult to perform. Rather than dismissing observational studies, we need to determine what circumstances may justify doing an observational study and when the study is sufficiently rigorous to be considered reasonably trustworthy. This article proposes criteria by which users of the literature might make such determinations. © 2016 Royal Australasian College of Physicians.

Peter Bourne's drug policy and the perils of a public health ethic, 1976-1978.

PubMed

Clark, Claire D; Dufton, Emily

2015-02-01

As President Jimmy Carter's advisor for health issues, Peter Bourne promoted a rational and comprehensive drug strategy that combined new supply-side efforts to prevent drug use with previously established demand-side addiction treatment programs. Using a public health ethic that allowed the impact of substances on overall population health to guide drug control, Bourne advocated for marijuana decriminalization as well as increased regulations for barbiturates. A hostile political climate, a series of rumors, and pressure from both drug legalizers and prohibitionists caused Bourne to resign in disgrace in 1978. We argue that Bourne's critics used his own public health framework to challenge him, describe the health critiques that contributed to Bourne's resignation, and present the story of his departure as a cautionary tale for today's drug policy reformers.

The rush to drill for natural gas: a public health cautionary tale.

PubMed

Finkel, Madelon L; Law, Adam

2011-05-01

Efforts to identify alternative sources of energy have focused on extracting natural gas from vast shale deposits. The Marcellus Shale, located in western New York, Pennsylvania, and Ohio, is estimated to contain enough natural gas to supply the United States for the next 45 years. New drilling technology-horizontal drilling and high-volume hydraulic fracturing of shale (fracking)-has made gas extraction much more economically feasible. However, this technique poses a threat to the environment and to the public's health. There is evidence that many of the chemicals used in fracking can damage the lungs, liver, kidneys, blood, and brain. We discuss the controversial technique of fracking and raise the issue of how to balance the need for energy with the protection of the public's health.

The Rush to Drill for Natural Gas: A Public Health Cautionary Tale

PubMed Central

Law, Adam

2011-01-01

Efforts to identify alternative sources of energy have focused on extracting natural gas from vast shale deposits. The Marcellus Shale, located in western New York, Pennsylvania, and Ohio, is estimated to contain enough natural gas to supply the United States for the next 45 years. New drilling technology—horizontal drilling and high-volume hydraulic fracturing of shale (fracking)—has made gas extraction much more economically feasible. However, this technique poses a threat to the environment and to the public's health. There is evidence that many of the chemicals used in fracking can damage the lungs, liver, kidneys, blood, and brain. We discuss the controversial technique of fracking and raise the issue of how to balance the need for energy with the protection of the public's health. PMID:21421959

Peter Bourne’s Drug Policy and the Perils of a Public Health Ethic, 1976–1978

PubMed Central

Dufton, Emily

2015-01-01

As President Jimmy Carter’s advisor for health issues, Peter Bourne promoted a rational and comprehensive drug strategy that combined new supply-side efforts to prevent drug use with previously established demand-side addiction treatment programs. Using a public health ethic that allowed the impact of substances on overall population health to guide drug control, Bourne advocated for marijuana decriminalization as well as increased regulations for barbiturates. A hostile political climate, a series of rumors, and pressure from both drug legalizers and prohibitionists caused Bourne to resign in disgrace in 1978. We argue that Bourne’s critics used his own public health framework to challenge him, describe the health critiques that contributed to Bourne’s resignation, and present the story of his departure as a cautionary tale for today’s drug policy reformers. PMID:25521893

Understanding Substance Use and Addiction Through the Lyrics of Black Sabbath: A Content Analysis.

PubMed

Conway, Kevin P; McGrain, Patrick

2016-10-14

Heavy metal music is distinguished for its deep sound and lyrical fixation with dark themes including war, destruction, doom, and misery. Such subjects permeate the music of Black Sabbath, the band generally considered the pioneers of heavy metal. One theme-substance use-is recurrent in Black Sabbath's songs and personal lives of its members. This study explored the band's relationship with substance use though a content analysis of all songs containing lyrics written and recorded in studio by Black Sabbath. The analysis included 156 songs across 19 albums recorded from 1970 to 2013. Three key findings emerged. First, a minority of songs (13%) contained substance references. Second, the songs with substance references were overwhelmingly (60%) negative, a pattern that increased over time. Third, despite many line-up changes over the band's 43-year period, every song referencing substance use except one featured vocalist Ozzy Osbourne and lyricist Geezer Butler. Contrary to the notion that heavy metal music glorifies or encourages substance use (Record Labeling, United States Senate, 1985), Black Sabbath's lyrics as a whole weave a cautionary tale of how persistent substance use can hijack free will, become the dominant focus of the affected individual, and produce myriad forms of human misery. The insidiousness of chronic substance use depicted by the lyrics mirrors findings from natural-history studies of individuals with substance use disorders and aligns with neurobiological heuristics of addiction.

Social Representation of Cyberbullying and Adolescent Suicide: A Mixed-Method Analysis of News Stories.

PubMed

Young, Rachel; Subramanian, Roma; Miles, Stephanie; Hinnant, Amanda; Andsager, Julie L

2017-09-01

Cyberbullying has provoked public concern after well-publicized suicides of adolescents. This mixed-methods study investigates the social representation of these suicides. A content analysis of 184 U.S. newspaper articles on death by suicide associated with cyberbullying or aggression found that few articles adhered to guidelines suggested by the World Health Organization and the American Foundation for Suicide Prevention to protect against suicidal behavioral contagion. Few articles made reference to suicide or bullying prevention resources, and most suggested that the suicide had a single cause. Thematic analysis of a subset of articles found that individual deaths by suicide were used as cautionary tales to prompt attention to cyberbullying. This research suggests that newspaper coverage of these events veers from evidence-based guidelines and that more work is needed to determine how best to engage with journalists about the potential consequences of cyberbullying and suicide coverage.

Ciprofloxacin and statin interaction: a cautionary tale of rhabdomyolysis.

PubMed

Goldie, Fraser Charles; Brogan, Amy; Boyle, James Graham

2016-07-28

A 62-year-old woman presented to hospital, on general practitioner (GP) advice, with a 15-day history of slowly progressing muscle weakness. Results showed newly deranged liver function and creatine kinase (CK) of >24 000. Prior medical history includes previous myocardial infarction and recurrent urinary tract infection. 4 days prior to symptom onset, the patient developed typical urinary tract infection symptoms, treated with ciprofloxacin. The patient had been taking simvastatin (40 mg nocte) for 13 years and had never previously taken ciprofloxacin. Initial management included intravenous crystalloid fluids and discontinuation of simvastatin. CK level fell, liver function slowly improved and renal function remained stable. Muscle weakness improved and the patient became independently able to perform activities of daily living. While the interactions between statins and other antibiotics are well documented, the interaction between statins and ciprofloxacin is less so. The consequences of this interaction can have potentially serious outcomes. 2016 BMJ Publishing Group Ltd.

Malthusian Parameters as Estimators of the Fitness of Microbes: A Cautionary Tale about the Low Side of High Throughput.

PubMed

Concepción-Acevedo, Jeniffer; Weiss, Howard N; Chaudhry, Waqas Nasir; Levin, Bruce R

2015-01-01

The maximum exponential growth rate, the Malthusian parameter (MP), is commonly used as a measure of fitness in experimental studies of adaptive evolution and of the effects of antibiotic resistance and other genes on the fitness of planktonic microbes. Thanks to automated, multi-well optical density plate readers and computers, with little hands-on effort investigators can readily obtain hundreds of estimates of MPs in less than a day. Here we compare estimates of the relative fitness of antibiotic susceptible and resistant strains of E. coli, Pseudomonas aeruginosa and Staphylococcus aureus based on MP data obtained with automated multi-well plate readers with the results from pairwise competition experiments. This leads us to question the reliability of estimates of MP obtained with these high throughput devices and the utility of these estimates of the maximum growth rates to detect fitness differences.

THE CHALLENGING ROLE OF A READING COACH, A CAUTIONARY TALE.

PubMed

Al Otaiba, Stephanie; Hosp, John L; Smartt, Susan; Dole, Janice A

2008-04-01

The purpose of this case study is to describe the challenges one coach faced during the initial implementation of a coaching initiative involving 33 teachers in an urban, high-poverty elementary school. Reading coaches are increasingly expected to play a key role in the professional development efforts to improve reading instruction in order to improve reading achievement for struggling readers. Data sources included initial reading scores for kindergarten and first-graders, pretest and posttest scores of teachers' knowledge, a teacher survey, focus group interviews, project documents, and field notes. Data were analyzed using a mixed methods approach. Findings revealed several challenges that have important implications for research and practice: that teachers encountered new information about teaching early reading that conflicted with their current knowledge, this new information conflicted with their core reading program, teachers had differing perceptions of the role of the reading coach that affected their feelings about the project, and reform efforts are time-intensive.

Assessing the validity of sales self-efficacy: a cautionary tale.

PubMed

Gupta, Nina; Ganster, Daniel C; Kepes, Sven

2013-07-01

We developed a focused, context-specific measure of sales self-efficacy and assessed its incremental validity against the broad Big 5 personality traits with department store salespersons, using (a) both a concurrent and a predictive design and (b) both objective sales measures and supervisory ratings of performance. We found that in the concurrent study, sales self-efficacy predicted objective and subjective measures of job performance more than did the Big 5 measures. Significant differences between the predictability of subjective and objective measures of performance were not observed. Predictive validity coefficients were generally lower than concurrent validity coefficients. The results suggest that there are different dynamics operating in concurrent and predictive designs and between broad and contextualized measures; they highlight the importance of distinguishing between these designs and measures in meta-analyses. The results also point to the value of focused, context-specific personality predictors in selection research. PsycINFO Database Record (c) 2013 APA, all rights reserved.

The search for biomarkers in the critically ill: a cautionary tale.

PubMed

Moran, John L; Solomon, Patricia J

2018-06-01

The search for biomarkers has been described as a dismal patchwork of fragmented research. We review biomarkers in sepsis in the critically ill in terms of conventional single circulating proteins. Despite sepsis biomarker publications trebling over the past 6 years, currently only one, procalcitonin, has materialised promise. We survey genomic biomarker initiatives, single nucleotide polymorphisms (SNPs) and gene signatures. Despite many SNP associations with sepsis susceptibility and a limited number of genome-wide association studies, the status of these associations is that of genomic signposts only. The standing of gene signatures in the paradigmatic discipline, breast cancer, is described. Uncertainties in the understanding of the sepsis process are documented - the dissociation between blood and tissue element activity, or compartmentalisation. The paradox of the active search for gene signatures to refine the sepsis phenotype and discover target subtypes for new therapies in the absence of such therapies is presented.

"Unreliability as a threat to understanding psychopathology: The cautionary tale of attentional bias": Correction to Rodebaugh et al. (2016).

PubMed

2016-10-01

Reports an error in "Unreliability as a threat to understanding psychopathology: The cautionary tale of attentional bias" by Thomas L. Rodebaugh, Rachel B. Scullin, Julia K. Langer, David J. Dixon, Jonathan D. Huppert, Amit Bernstein, Ariel Zvielli and Eric J. Lenze ( Journal of Abnormal Psychology , 2016[Aug], Vol 125[6], 840-851). There was an error in the Author Note concerning the support of the MacBrain Face Stimulus Set. The correct statement is provided. (The following abstract of the original article appeared in record 2016-30117-001.) The use of unreliable measures constitutes a threat to our understanding of psychopathology, because advancement of science using both behavioral and biologically oriented measures can only be certain if such measurements are reliable. Two pillars of the National Institute of Mental Health's portfolio-the Research Domain Criteria (RDoC) initiative for psychopathology and the target engagement initiative in clinical trials-cannot succeed without measures that possess the high reliability necessary for tests involving mediation and selection based on individual differences. We focus on the historical lack of reliability of attentional bias measures as an illustration of how reliability can pose a threat to our understanding. Our own data replicate previous findings of poor reliability for traditionally used scores, which suggests a serious problem with the ability to test theories regarding attentional bias. This lack of reliability may also suggest problems with the assumption (in both theory and the formula for the scores) that attentional bias is consistent and stable across time. In contrast, measures accounting for attention as a dynamic process in time show good reliability in our data. The field is sorely in need of research reporting findings and reliability for attentional bias scores using multiple methods, including those focusing on dynamic processes over time. We urge researchers to test and report reliability of all measures, considering findings of low reliability not just as a nuisance but as an opportunity to modify and improve upon the underlying theory. Full assessment of reliability of measures will maximize the possibility that RDoC (and psychological science more generally) will succeed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Molecular-genetic correlates of infant attachment: A cautionary tale

PubMed Central

Booth-Laforce, Cathryn; Belsky, Jay; Burt, Keith B.; Groh, Ashley M.

2014-01-01

This paper advises caution in relation to the increasing interest in molecular-genetic association studies in developmental psychology based on a set of empirical examples from the NICHD Study of Early Child Care and Youth Development (SECCYD) that highlight the fragility of effects reported in the literature on the molecular-genetic correlates of infant attachment. Specifically, this paper updates and provides three extensions to results reported in Luijk et al. (2011), which recently failed to replicate evidence from smaller-sample studies that a set of dopaminergic, serotonergic, and oxytonergic markers are significantly associated with infant attachment security or disorganization. First, we report here that the average effect of “usual suspect” polymorphisms on infant attachment security and disorganization in the SECCYD is approximately zero. Second, because Luijk et al. (2011) reported data based exclusively on the White infants in the SECCYD, this paper reveals that the average effect of polymorphisms featured in this literature is also of trivial magnitude in the non-White sub-sample (cf. Chen, Barth, Johnson, Gotlib, & Johnson, 2011). Third, this paper attempts, but fails, to replicate a recent finding by Raby et al. (2012) suggesting that, although molecular-genetic polymorphisms might not be implicated in security versus insecurity, the serotonin transporter gene contributes to variation in emotional distress during the Strange Situation Procedure. Implications for future research on the genetics of developmental phenotypes in general and attachment in particular are discussed, with a focus on statistical power and model-based theory testing. PMID:23421800

A Fairy-Tale Landscape

NASA Image and Video Library

2008-05-29

Fun, fairy-tale nicknames have been assigned to features in this animated view of the workspace reachable by the robotic arm of NASA Phoenix Mars Lander. For example, Sleepy Hollow denotes a trench and Headless designates a rock.

Context influences on TALE-DNA binding revealed by quantitative profiling.

PubMed

Rogers, Julia M; Barrera, Luis A; Reyon, Deepak; Sander, Jeffry D; Kellis, Manolis; Joung, J Keith; Bulyk, Martha L

2015-06-11

Transcription activator-like effector (TALE) proteins recognize DNA using a seemingly simple DNA-binding code, which makes them attractive for use in genome engineering technologies that require precise targeting. Although this code is used successfully to design TALEs to target specific sequences, off-target binding has been observed and is difficult to predict. Here we explore TALE-DNA interactions comprehensively by quantitatively assaying the DNA-binding specificities of 21 representative TALEs to ∼5,000-20,000 unique DNA sequences per protein using custom-designed protein-binding microarrays (PBMs). We find that protein context features exert significant influences on binding. Thus, the canonical recognition code does not fully capture the complexity of TALE-DNA binding. We used the PBM data to develop a computational model, Specificity Inference For TAL-Effector Design (SIFTED), to predict the DNA-binding specificity of any TALE. We provide SIFTED as a publicly available web tool that predicts potential genomic off-target sites for improved TALE design.

Minimal barcode distance between two water mite species from Madeira Island: a cautionary tale.

PubMed

García-Jiménez, Ricardo; Horreo, Jose Luis; Valdecasas, Antonio G

2017-06-01

In this work, we compare morphological and molecular data in their ability to distinguish between species of water mites (Acari, Prostigmata, Hydrachnidia). We have focused on the two species of the genus Lebertia inhabiting the island of Madeira. While traditional morphological traits were initially sufficient to distinguish between these two species, the molecular data were more dependable on the kind of analysis carried out. Single arbitrary genetic distance (e.g. a K2P distance below 2%) may lead to the conclusion that the specimens under study belong to the same species. Analysing the same specimens with the coalescent model has proved the evolutionary independence of both Lebertia clades in Madeira. Furthermore, multi-rate Poisson Tree Process analysis confirmed both lineages as independent species. Our results agree with previous studies warning of the dangers of rigid species delimitation based on arbitrary molecular distances. In addition, the importance of different molecular data approaches for correct species delimitation in water mites is highlighted.

Prolonged spontaneous normocalcaemia in pseudohypoparathyroidism from resorption of soft tissue calcium deposits: a cautionary tale

PubMed Central

Carter, Erin E; Kline, Gregory

2014-01-01

A 42-year-old man diagnosed with pseudohypoparathyroidism and Albright's hereditary osteodystrophy as an infant was lost to follow-up and remained, unmonitored, on calcitriol and calcium for over 20 years. He presented after having an ST-elevation myocardial infarction. In addition to coronary artery calcifications, he was found to have diffuse subcutaneous and joint calcifications. His calcium, phosphate and parathyroid hormone (PTH) levels were normal, and given the lack of prior documentation in the diagnosis he was instructed to discontinue calcitriol and calcium until further investigations were completed. Despite stopping the medication, his serum calcium remained normal for over 1 year. It was not until 18 months later, when his soft tissue calcium stores were depleted, that he finally developed symptomatic hypocalcaemia and an elevated PTH. This case not only emphasises the importance of long-term follow-up for patients with pseudohypoparathyroidism, but also highlights the potential complications of long-term, unmonitored, calcitriol use. PMID:24481017

Caffeine Toxicity Due to Supplement Use in Caffeine--Naïve Individual: A Cautionary Tale.

PubMed

Lystrup, Robert M; Leggit, Jeffery C

2015-08-01

Thousands of military members self-medicate with dietary supplements containing unknown quantities of pharmacologically active compounds. These poorly regulated substances can cause real harm to the military population, especially when they contain stimulants such as caffeine. When taken regularly, caffeine has several performance-enhancing benefits. However, when used excessively or in vulnerable populations, caffeine can cause several unwanted side effects such as nervousness, sensory disturbances, insomnia, arrhythmia, excitability, inattentiveness, restlessness, mood changes, gastrointestinal disturbances, and even psychosis. Vulnerable patients include the caffeine-naïve, physiologically stressed, young, and mentally ill patients. One such case describes a caffeine-naïve service member who suffered an adverse reaction after taking an allegedly moderate dose of caffeine from a pill he obtained from a teammate. This case highlights the importance of supplement awareness among service members, increased provider vigilance, third party verification, and enhanced regulation on the approval and marketing of dietary supplements. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

A Cautionary Tale: Examining the Interplay of Culturally Specific Risk and Resilience Factors in Indigenous Communities

PubMed Central

Walls, Melissa L.; Whitbeck, Les; Armenta, Brian

2016-01-01

Efforts to build empirical evidence for the protective effects of Indigenous cultural factors on psychological health have yielded mixed findings. We examine the interplay of previously hypothesized culturally relevant risk (discrimination, historical loss) and protective (spiritual activities) factors among Indigenous people. The sample includes 569 Indigenous adolescents (M age = 17.23, SD = 0.88; 51.0% girls) and 563 Indigenous adult caregivers (M age = 44.66, SD = 9.18; 77.4% women). Our central finding was that indigenous spirituality was associated with poorer psychological outcomes across several domains (depressive symptoms, anger, anxiety, somatization and interpersonal difficulties), but observed effects were attenuated once perceived discrimination and historical losses were added to statistical models. Thus, consideration of relevant stressors drastically changed our conclusions, underscoring the uncertain dynamics through which specific Indigenous cultural factors impact mental health. Researchers should work in collaboration with Indigenous communities to improve measurement and empirical investigation of these complex constructs. PMID:28138417

THE CHALLENGING ROLE OF A READING COACH, A CAUTIONARY TALE

PubMed Central

AL OTAIBA, STEPHANIE; HOSP, JOHN L.; SMARTT, SUSAN; DOLE, JANICE A.

2011-01-01

The purpose of this case study is to describe the challenges one coach faced during the initial implementation of a coaching initiative involving 33 teachers in an urban, high-poverty elementary school. Reading coaches are increasingly expected to play a key role in the professional development efforts to improve reading instruction in order to improve reading achievement for struggling readers. Data sources included initial reading scores for kindergarten and first-graders, pretest and posttest scores of teachers’ knowledge, a teacher survey, focus group interviews, project documents, and field notes. Data were analyzed using a mixed methods approach. Findings revealed several challenges that have important implications for research and practice: that teachers encountered new information about teaching early reading that conflicted with their current knowledge, this new information conflicted with their core reading program, teachers had differing perceptions of the role of the reading coach that affected their feelings about the project, and reform efforts are time-intensive. PMID:23794791

Contrasting molecular and morphological evidence for the identification of an anomalous Buteo: a cautionary tale for hybrid diagnosis

PubMed Central

2017-01-01

An adult Buteo was found dead as a road-kill south of Sacramento, California, and was thought to represent the first state record of the eastern Red-shouldered Hawk (B. lineatus lineatus;). It is now a specimen in the Museum of Wildlife and Fisheries Biology (WFB 4816) at the University of California, Davis. We examined this specimen and found that many of its plumage characters differed from all other adult Red-shouldered Hawks examined, including nominate adults. Plumage markings and measurements were intermediate between Red-tailed Hawk (Buteo jamaicensis, ssp calurus) and Red-shouldered Hawk (ssp elegans), leading us to hypothesize that the bird was a hybrid. However, mtDNA sequences and nuDNA microsatellites proved definitively that the bird was a Red-shouldered Hawk, most likely of eastern origin. This case illustrates that apparent hybrids or apparent vagrants could be individuals with anomalous phenotypes caused by rare genetic variation or novel epigenetic effects. PMID:28097061

Exploring the Complexities of Group Work in Science Class: a Cautionary tale of Voice and Equitable Access to Resources for Learning

NASA Astrophysics Data System (ADS)

Richmond, Gail

The interactions of 2 focus students with others in their cooperative base groups were examined as the students designed, carried out, and interpreted scientific investigations. These 2 students differed with respect to race, gender, socioeconomic status, and academic achievement. They were alike in that both maintained high levels of motivation and interaction with the scientific problems they faced. Their group interactions were not entirely positive, and the difficulties and inequities they faced are described. The data make manifest that group work is a complex process; educators must be sensitive and responsive to the subtle ways understanding can be enhanced or undermined as a result of group dynamics, which are in turn determined by individual expectations - often unfounded - of others' capacities and behaviors, and perceptions of desired group and individual outcomes. These observations also have implications for how educators help prepare prospective teachers to develop effective pedagogical strategies for teaching diverse students.

Extrinsic origins of the apparent relaxorlike behavior in CaCu3Ti4O12 ceramics at high temperatures: A cautionary tale

NASA Astrophysics Data System (ADS)

Li, Ming; Sinclair, Derek C.; West, Anthony R.

2011-04-01

Although the origins of the high effective permittivity observed in CaCu3Ti4O12 (CCTO) ceramics and single crystals at ˜100-400 K have been resolved, the relaxorlike temperature- and frequency-dependence of permittivity obtained from fixed frequency capacitance measurements at higher temperatures reported in the literature remains unexplained, especially as CCTO adopts a centrosymmetric cubic crystal structure in the range of ˜35-1273 K. Impedance spectroscopy studies reveal that this type of relaxorlike behavior is an artifact induced mainly by a nonohmic sample-electrode contact impedance. In addition, an instrument-related parasitic series inductance and resistance effect modifies the measured capacitance values as the sample resistance decreases with increasing temperature. This can lead to an underestimation of the sample capacitance and, in extreme cases, to so-called `negative capacitance.' Such a relaxorlike artifact and negative capacitance behavior are not unique to CCTO and may be expected in other leaky dielectrics whose resistance is low.

Biological Assessment of Newfoundland Rivers Based on the Depauperate Macroinvertebrate Fauna With Emphasis on the Mayfly, Stonefly and Caddisfly Fauna: a Cautionary Tale.

NASA Astrophysics Data System (ADS)

Colbo, M. H.; Cote, D.; Kendall, V.

2005-05-01

The fauna of insular Newfoundland compared to the mainland is depauperate, e.g., 35 spp of mayflies versus about 160 spp in Maine. The question is can this depauperate fauna provide good biomonitoring information? A comparative study using present /absent data from 85 sites in eastern Newfoundland was analyzed with particular reference to the Ephemeroptera, Plecoptera and Trichoptera fauna. The results indicated these data did differentiate regions sampling type and land use when run through a simple Principle Component Analysis (PCA). The PCA 1 and 2 components varied from no to a strong correlation with both Ephemeroptera and Trichoptera richness and taxa richness of the major feeding groups. However, applying previously published biotic indices of species that occur in Newfoundland did not provide satisfactory results. It appears these indices may reflect oxygen gradients rather than pollutant concentrations and in our cold well oxygenated streams yield unsatisfactory discrimination among natural and perturb streams.

Social capital and basic goods: the cautionary tale of drinking water in India.

PubMed

Motiram, Sripad; Osberg, Lars

2010-01-01

This study uses micro-data from the 1998-99 Indian Time Use Survey (ITUS; covering 77,593 persons in 18,591 households in Gujarat, Tamil Nadu, Madhya Pradesh, Meghalaya, Orissa, and Haryana) to argue that time use data provides a natural metric for measuring "social capital" building activities and for distinguishing between the relative importance of "bonding" into groups or "bridging" within communities. The study examines the correlation between inequality in landownership, caste status, measures of local social capital, and whether or not a household will have to collect water. In India, the probability that a rural household fetches water is 4.8% and 9.1% lower in communities in which the average time spent on social interaction and community-based activities at the district-level doubles, but it is 18.9% greater when the time in group-based activities doubles. Inequalities in landownership and home ownership are associated with considerably larger differences in local tap water availability.

Back to the future: a history of ACOG in social media's golden age.

PubMed

DeNicola, Nathaniel; Good, Meadow; Newton, Luke

2014-12-01

To chronicle a medical professional society's adoption of innovation and to describe themes pertinent to the adoption. In September 2013, the American College of Obstetricians and Gynecologists (ACOG) published a Committee Opinion on Toxic Environmental Agents that included an infographic and social media awareness campaign. To date, it claims one of the highest total audience reaches for an ACOG Facebook post reaching nearly 18 000 viewers. Despite this powerful promise, ACOG's timely and successful social media campaign did not always appear an obvious strategy. Although social media took hold of popular culture in the early 2000s, social media's professional etiquette remained uncharted and rife, with cautionary tales through the latter half of the decade. Through a thoughtful and dedicated process, the ACOG Fellow and Junior Fellow leadership partnered to navigate the appropriate balance of innovation and prudence that propelled ACOG into social media's golden age, and paved the pathway for more progressive institutional changes.

A Mood Management Intervention in an Internet Stop Smoking Randomized Controlled Trial Does Not Prevent Depression: A Cautionary Tale

PubMed Central

Schueller, Stephen M.; Pérez-Stable, Eliseo J.; Muñoz, Ricardo F.

2014-01-01

Smoking and depression are related, and mood management interventions included in smoking cessation interventions can increase smoking abstinence rates. Could a mood management intervention embedded in an Internet-based smoking cessation intervention prevent major depressive episodes? Spanish- and English-speaking smokers (N = 17,430) from 191 countries were randomized to one of four online self-help intervention conditions (two with mood management). We analyzed preventive effects among those participants without a major depressive episode at baseline. The mood management intervention did not reduce the incidence of major depressive episodes in the following 12 months. However, we found a mood management by depression risk interaction (OR = 1.77, p = .004), such that high-risk participants who received the mood management intervention had an increased occurrence of major depressive episodes (32.8% vs. 26.6%), but not low-risk participants (11.6% vs. 10.8%). Further research on whether mood management interventions may have deleterious effects on subsets of smokers appears warranted. PMID:25525565

A cautionary tale on the use of antiplatelet treatment following TURP.

PubMed

Murray, Aileen Marie; Keville, Norah; Gray, Sam

2014-04-04

A pleasant 74-year-old man was discharged home following a complication-free transurethral resection of his prostate (TURP) and successful trial without catheter. Unfortunately, on postoperative day 6, he presented to A&E with chest pain requiring emergency intervention for a confirmed myocardial infarction. A drug-eluting stent was inserted into his right coronary artery and he was started on dual antiplatelet therapy of aspirin and clopidogrel. On day 7, the patient developed significant haematuria requiring transfusion and an obstructive uropathy, requiring an emergency laparotomy and 1 L of organised clot evacuation from his bladder. The dual antiplatelet treatment was restarted on day 4 postlaparotomy, following debate between both the cardiology and urology teams regarding its appropriate reintroduction. On day 7, he was rushed back to the theatre for a re-laparotomy after CT confirmed reaccumulation of clot following an acute deterioration at ward level. The patient made an excellent recovery and was discharged home with regular outpatient follow-up.

Retrofits we`d rather forget

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

Hurrelbrinck, N.

1996-01-01

We all make mistakes, and the best of us make some of the biggest and best ones. An energy service company in New York installed light sensitive thermostats in a complex where the residents covered windows with heavy curtains to curtail air leakage. A crew in Chicago forgot to place a top plate in the top floor bathroom of a multifamily building; when they blew insulation into the roof, it filled the bathroom. A state official in the Midwest was inspecting the attic insulation in an FHA house when his foot slipped off the walk board and went through themore » ceiling drywall. And weatherization experts in Pittsburgh have discovered that a blower door can fill a house with decades` worth of accumulated soot. These mishaps could visit anyone. Much as those visited would rather bury them, we think they deserve an airing on the pages of Home Energy. In this issue, we present some cautionary tales from the elites of insulation.« less

Barriers to Achieving Economies of Scale in Analysis of EHR Data. A Cautionary Tale.

PubMed

Sendak, Mark P; Balu, Suresh; Schulman, Kevin A

2017-08-09

Signed in 2009, the Health Information Technology for Economic and Clinical Health Act infused $28 billion of federal funds to accelerate adoption of electronic health records (EHRs). Yet, EHRs have produced mixed results and have even raised concern that the current technology ecosystem stifles innovation. We describe the development process and report initial outcomes of a chronic kidney disease analytics application that identifies high-risk patients for nephrology referral. The cost to validate and integrate the analytics application into clinical workflow was $217,138. Despite the success of the program, redundant development and validation efforts will require $38.8 million to scale the application across all multihospital systems in the nation. We address the shortcomings of current technology investments and distill insights from the technology industry. To yield a return on technology investments, we propose policy changes that address the underlying issues now being imposed on the system by an ineffective technology business model.

Technological Change in Assessing Economics: A Cautionary Welcome

ERIC Educational Resources Information Center

Kennelly, Brendan; Considine, John; Flannery, Darragh

2009-01-01

The use of computer-based automated assignment systems in economics has expanded significantly in recent years. The most widely used system is Aplia which was developed by Paul Romer in 2000. Aplia is a computer application designed to replace traditional paper-based assignments in economics. The main features of Aplia are: (1) interactive content…

Programmable DNA-binding proteins from Burkholderia provide a fresh perspective on the TALE-like repeat domain

PubMed Central

de Lange, Orlando; Wolf, Christina; Dietze, Jörn; Elsaesser, Janett; Morbitzer, Robert; Lahaye, Thomas

2014-01-01

The tandem repeats of transcription activator like effectors (TALEs) mediate sequence-specific DNA binding using a simple code. Naturally, TALEs are injected by Xanthomonas bacteria into plant cells to manipulate the host transcriptome. In the laboratory TALE DNA binding domains are reprogrammed and used to target a fused functional domain to a genomic locus of choice. Research into the natural diversity of TALE-like proteins may provide resources for the further improvement of current TALE technology. Here we describe TALE-like proteins from the endosymbiotic bacterium Burkholderia rhizoxinica, termed Bat proteins. Bat repeat domains mediate sequence-specific DNA binding with the same code as TALEs, despite less than 40% sequence identity. We show that Bat proteins can be adapted for use as transcription factors and nucleases and that sequence preferences can be reprogrammed. Unlike TALEs, the core repeats of each Bat protein are highly polymorphic. This feature allowed us to explore alternative strategies for the design of custom Bat repeat arrays, providing novel insights into the functional relevance of non-RVD residues. The Bat proteins offer fertile grounds for research into the creation of improved programmable DNA-binding proteins and comparative insights into TALE-like evolution. PMID:24792163

Promise and Challenge of Identifying Threshold Concepts: A Cautionary Account of Using Transactional Curriculum Inquiry

ERIC Educational Resources Information Center

Barradell, Sarah; Peseta, Tai

2016-01-01

The original work on threshold concepts arose from a project designed to improve students' learning experiences by taking seriously the features of disciplinary knowledge as its starting point. The conceptual and empirical work on threshold concepts has since developed and matured. While many disciplines have engaged enthusiastically with the…

A TALE-inspired computational screen for proteins that contain approximate tandem repeats.

PubMed

Perycz, Malgorzata; Krwawicz, Joanna; Bochtler, Matthias

2017-01-01

TAL (transcription activator-like) effectors (TALEs) are bacterial proteins that are secreted from bacteria to plant cells to act as transcriptional activators. TALEs and related proteins (RipTALs, BurrH, MOrTL1 and MOrTL2) contain approximate tandem repeats that differ in conserved positions that define specificity. Using PERL, we screened ~47 million protein sequences for TALE-like architecture characterized by approximate tandem repeats (between 30 and 43 amino acids in length) and sequence variability in conserved positions, without requiring sequence similarity to TALEs. Candidate proteins were scored according to their propensity for nuclear localization, secondary structure, repeat sequence complexity, as well as covariation and predicted structural proximity of variable residues. Biological context was tentatively inferred from co-occurrence of other domains and interactome predictions. Approximate repeats with TALE-like features that merit experimental characterization were found in a protein of chestnut blight fungus, a eukaryotic plant pathogen.

A TALE-inspired computational screen for proteins that contain approximate tandem repeats

PubMed Central

Krwawicz, Joanna

2017-01-01

TAL (transcription activator-like) effectors (TALEs) are bacterial proteins that are secreted from bacteria to plant cells to act as transcriptional activators. TALEs and related proteins (RipTALs, BurrH, MOrTL1 and MOrTL2) contain approximate tandem repeats that differ in conserved positions that define specificity. Using PERL, we screened ~47 million protein sequences for TALE-like architecture characterized by approximate tandem repeats (between 30 and 43 amino acids in length) and sequence variability in conserved positions, without requiring sequence similarity to TALEs. Candidate proteins were scored according to their propensity for nuclear localization, secondary structure, repeat sequence complexity, as well as covariation and predicted structural proximity of variable residues. Biological context was tentatively inferred from co-occurrence of other domains and interactome predictions. Approximate repeats with TALE-like features that merit experimental characterization were found in a protein of chestnut blight fungus, a eukaryotic plant pathogen. PMID:28617832

Programmable DNA-binding proteins from Burkholderia provide a fresh perspective on the TALE-like repeat domain.

PubMed

de Lange, Orlando; Wolf, Christina; Dietze, Jörn; Elsaesser, Janett; Morbitzer, Robert; Lahaye, Thomas

2014-06-01

The tandem repeats of transcription activator like effectors (TALEs) mediate sequence-specific DNA binding using a simple code. Naturally, TALEs are injected by Xanthomonas bacteria into plant cells to manipulate the host transcriptome. In the laboratory TALE DNA binding domains are reprogrammed and used to target a fused functional domain to a genomic locus of choice. Research into the natural diversity of TALE-like proteins may provide resources for the further improvement of current TALE technology. Here we describe TALE-like proteins from the endosymbiotic bacterium Burkholderia rhizoxinica, termed Bat proteins. Bat repeat domains mediate sequence-specific DNA binding with the same code as TALEs, despite less than 40% sequence identity. We show that Bat proteins can be adapted for use as transcription factors and nucleases and that sequence preferences can be reprogrammed. Unlike TALEs, the core repeats of each Bat protein are highly polymorphic. This feature allowed us to explore alternative strategies for the design of custom Bat repeat arrays, providing novel insights into the functional relevance of non-RVD residues. The Bat proteins offer fertile grounds for research into the creation of improved programmable DNA-binding proteins and comparative insights into TALE-like evolution. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Ausgerechnet "Rumpelstilzchen?" Grimms Marchen im DaF-Unterricht (Really Rumpelstilskin? Grimm's Fairy Tales in German as a Foreign Language Instruction).

ERIC Educational Resources Information Center

Weber, Hans

2000-01-01

Suggests the use of fairy tales in German foreign language instruction at the intermediate level. This suggestion is established using features of the Grimm genre and clarified using concrete examples. (Author/DMK)

Telling Tales over Time: Constructing and Deconstructing the School Calendar

ERIC Educational Resources Information Center

Weiss, Joel; Brown, Robert S.

2003-01-01

The September-to-June school calendar has been a fixture of North America for almost a century. Its origins have usually been told as an unexamined tale attributed to features of nineteenth century rural society. We challenge this interpretation by suggesting that multiple pressures arising from increasing urbanization influenced its roots. We…

Limitations in the Prediction of Mass Violence: Cautionary Tales.

PubMed

Archer, Robert P

2018-06-21

The incidents of mass violence that have occurred in the United States have been deeply disturbing to the public as well as to mental health professionals. The public, the media, as well as our patients, family members, and friends have reached out to mental health professionals in the hope that we can provide an understanding of these events that might serve to reduce their frequency in the future. This article explores how we can best respond to these requests, including the current limitations of psychologists in the prediction of mass violence. Two incidents of mass violence are used to illustrate these issues. The first is a review of the investigation of the explosion on the U.S.S. Iowa in April 1989 that resulted in the deaths of 47 seamen. The second incident used for illustration purposes will be the University of Texas Clock Tower shootings that occurred in August 1968. This article discusses the reliability and validity problems inherent in retrospective reviews of the personality characteristics of perpetrators, and the limitations imposed by base-rate issues in the prediction of mass violence.

Use of dietary supplements and hormones in adolescents: A cautionary tale

PubMed Central

Guyda, Harvey J

2005-01-01

Ergogenic aids, such as nutritional supplements, anabolic steroids and human growth hormone, are increasingly being used to enhance sports performance or body image. While few rigorous scientific studies have derived significant conclusions, the marketing and promotion of most supplements is intense and far exceeds the data supporting their use. Particular concern has arisen regarding safety in the use of these substances among adolescents, who may be at particular risk when using caffeine-ephedra and anabolic steroid combinations. Indeed, long-term effects and fatalities have been reported. As a consequence, the American Academy of Pediatrics has condemned the use of anabolic steroid use for bodybuilding or performance enhancement in adolescents. Health care professionals need to educate themselves about ergogenic use and ask informed questions of their adolescent patients. An honest discussion of the limitations of most supplements, and acknowledgement that some supplements may work some of the time, may allow the physician to be more credible and useful in providing medical care and guidance to the adolescent seeking to improve body image or athletic performance. PMID:19668667

In vivo evolution of antimicrobial resistance in a series of Staphylococcus aureus patient isolates: the entire picture or a cautionary tale?

PubMed Central

van Hal, Sebastiaan J.; Steen, Jason A.; Espedido, Björn A.; Grimmond, Sean M.; Cooper, Matthew A.; Holden, Matthew T. G.; Bentley, Stephen D.; Gosbell, Iain B.; Jensen, Slade O.

2014-01-01

Objectives To obtain an expanded understanding of antibiotic resistance evolution in vivo, particularly in the context of vancomycin exposure. Methods The whole genomes of six consecutive methicillin-resistant Staphylococcus aureus blood culture isolates (ST239-MRSA-III) from a single patient exposed to various antimicrobials (over a 77 day period) were sequenced and analysed. Results Variant analysis revealed the existence of non-susceptible sub-populations derived from a common susceptible ancestor, with the predominant circulating clone(s) selected for by type and duration of antimicrobial exposure. Conclusions This study highlights the dynamic nature of bacterial evolution and that non-susceptible sub-populations can emerge from clouds of variation upon antimicrobial exposure. Diagnostically, this has direct implications for sample selection when using whole-genome sequencing as a tool to guide clinical therapy. In the context of bacteraemia, deep sequencing of bacterial DNA directly from patient blood samples would avoid culture ‘bias’ and identify mutations associated with circulating non-susceptible sub-populations, some of which may confer cross-resistance to alternate therapies. PMID:24047554

In vivo evolution of antimicrobial resistance in a series of Staphylococcus aureus patient isolates: the entire picture or a cautionary tale?

PubMed

van Hal, Sebastiaan J; Steen, Jason A; Espedido, Björn A; Grimmond, Sean M; Cooper, Matthew A; Holden, Matthew T G; Bentley, Stephen D; Gosbell, Iain B; Jensen, Slade O

2014-02-01

To obtain an expanded understanding of antibiotic resistance evolution in vivo, particularly in the context of vancomycin exposure. The whole genomes of six consecutive methicillin-resistant Staphylococcus aureus blood culture isolates (ST239-MRSA-III) from a single patient exposed to various antimicrobials (over a 77 day period) were sequenced and analysed. Variant analysis revealed the existence of non-susceptible sub-populations derived from a common susceptible ancestor, with the predominant circulating clone(s) selected for by type and duration of antimicrobial exposure. This study highlights the dynamic nature of bacterial evolution and that non-susceptible sub-populations can emerge from clouds of variation upon antimicrobial exposure. Diagnostically, this has direct implications for sample selection when using whole-genome sequencing as a tool to guide clinical therapy. In the context of bacteraemia, deep sequencing of bacterial DNA directly from patient blood samples would avoid culture 'bias' and identify mutations associated with circulating non-susceptible sub-populations, some of which may confer cross-resistance to alternate therapies.

The peopling of Europe and the cautionary tale of Y chromosome lineage R-M269

PubMed Central

Busby, George B. J.; Brisighelli, Francesca; Sánchez-Diz, Paula; Ramos-Luis, Eva; Martinez-Cadenas, Conrado; Thomas, Mark G.; Bradley, Daniel G.; Gusmão, Leonor; Winney, Bruce; Bodmer, Walter; Vennemann, Marielle; Coia, Valentina; Scarnicci, Francesca; Tofanelli, Sergio; Vona, Giuseppe; Ploski, Rafal; Vecchiotti, Carla; Zemunik, Tatijana; Rudan, Igor; Karachanak, Sena; Toncheva, Draga; Anagnostou, Paolo; Ferri, Gianmarco; Rapone, Cesare; Hervig, Tor; Moen, Torolf; Wilson, James F.; Capelli, Cristian

2012-01-01

Recently, the debate on the origins of the major European Y chromosome haplogroup R1b1b2-M269 has reignited, and opinion has moved away from Palaeolithic origins to the notion of a younger Neolithic spread of these chromosomes from the Near East. Here, we address this debate by investigating frequency patterns and diversity in the largest collection of R1b1b2-M269 chromosomes yet assembled. Our analysis reveals no geographical trends in diversity, in contradiction to expectation under the Neolithic hypothesis, and suggests an alternative explanation for the apparent cline in diversity recently described. We further investigate the young, STR-based time to the most recent common ancestor estimates proposed so far for R-M269-related lineages and find evidence for an appreciable effect of microsatellite choice on age estimates. As a consequence, the existing data and tools are insufficient to make credible estimates for the age of this haplogroup, and conclusions about the timing of its origin and dispersal should be viewed with a large degree of caution. PMID:21865258

Frequency of whole breast radiation therapy after intraoperative radiation therapy due to criteria identified by lumpectomy.

PubMed

Mellon, Eric A; Orman, Amber; Joya, Luis E; Montejo, Michael E; Laronga, Christine; Hoover, Susan J; Lee, M Catherine; Khakpour, Nazanin; Kubal, Pamela F; Diaz, Roberto

For selected early breast cancers, intraoperative radiation therapy (IORT) at the time of lumpectomy can be an efficient alternative to fractionated whole breast radiation therapy (WBRT). However, some patients are later recommended WBRT after IORT due to surgical pathologic findings. To understand risk factor identification rates triggering WBRT recommendation, we analyzed adverse prognostic features based on multiple international criteria for suitability for accelerated partial breast irradiation. We performed a single-institution retrospective review of all 200 nonrecurrent invasive breast carcinomas that received IORT in 20 Gy to the tumor cavity using a 50 kV photon applicator between January 2011 and December 2015. IORT eligibility was based on the 2009 accelerated partial breast irradiation Consensus Statement from the American Society for Radiation Oncology (ASTRO). IORT was offered as the sole radiation modality to patients meeting 0-1 "cautionary" and no "unsuitable" criteria before lumpectomy. WBRT was recommended after IORT when 2+ cautionary and/or 1+ unsuitable criteria were met after accounting for resection pathology. We recalculated WBRT recommendation rates using initial and reresection margins for ASTRO consensus, Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology recommendations, and TARGeted Intraoperative radioTherapy vs. Postoperative Radiotherapy trial "prepathology" stratum protocol. Depending on the selection criteria chosen, rates of WBRT recommendation can vary from 4.5% to 33%. WBRT recommendation rates of 30-33% after lumpectomy and IORT are observed when the WBRT indication is a single ASTRO cautionary/unsuitable, Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology intermediate/high-risk criterion, or TARGeted Intraoperative radioTherapy vs. postoperative radiotherapy trial protocol recommendation. Alternatively, allowing for re-excision to clear margins and accepting one ASTRO cautionary factor lowered the rate of WBRT recommendation to 9.5%. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Biomass-C specific temperature responses of microbial C transformations reveal consistency regardless of microbial community structure across diverse timescales of inquiry

NASA Astrophysics Data System (ADS)

Min, K.; Buckeridge, K. M.; Ziegler, S. E.; Edwards, K. A.; Bagchi, S.; Billings, S. A.

2016-12-01

The responses of heterotrophic microbial process rates to temperature in soils are often investigated in the short-term (hours to months), making it difficult to predict longer-term temperature responses. Here, we integrate the temperature sensitivity obtained from the Arrhenius model with the concepts of microbial resistance, resilience, and susceptibility to assess temporal dynamics of microbial temperature responses. We collected soils along a boreal forest climate gradient (long-term effect), and quantified exo-enzyme activities and CO2 respiration at 5, 15, and 25°C for 84 days (relatively short-term effect). Microbial process rates were examined at two levels (per g microbial biomass-C; and per g dry soil) along with community structure, to characterize driving mechanisms for temporal patterns (e.g., size of biomass, physiological plasticity, community composition). Although temperature sensitivity of exo-enzyme activities on a per g dry soil basis showed both resistance and resilience depending on the types of exo-enzyme, biomass -C-specific responses always exhibited resistance regardless of distinct community composition. Temperature sensitivity of CO2 respiration was constant across time and different communities at both units. This study advances our knowledge in two ways. First, resistant temperature sensitivity of exo-enzymes and respiration at biomass-C specific level across distinct communities and diverse timescales indicates a common relationship between microbial physiology and temperature at a fundamental level, a useful feature allowing microbial process models to be reasonably simplified. Second, different temporal responses of exo-enzymes depending on the unit selected provide a cautionary tale for those projecting future microbial behaviors, because interpretation of ecosystem process rates may vary with the unit of observation.

A cautionary tale: A study of a methane enhancement over the North Sea

NASA Astrophysics Data System (ADS)

Cain, M.; Warwick, N. J.; Fisher, R. E.; Lowry, D.; Lanoisellé, M.; Nisbet, E. G.; France, J.; Pitt, J.; O'Shea, S.; Bower, K. N.; Allen, G.; Illingworth, S.; Manning, A. J.; Bauguitte, S.; Pisso, I.; Pyle, J. A.

2017-07-01

Airborne measurements of a methane (CH4) plume over the North Sea from August 2013 are analyzed. The plume was only observed downwind of circumnavigated gas fields, and three methods are used to determine its source. First, a mass balance calculation assuming a gas field source gives a CH4 emission rate between 2.5 ± 0.8×104 and 4.6 ± 1.5×104 kg h-1. This would be greater than the industry's reported 0.5% leak rate if it were emitting for more than half the time. Second, annual average UK CH4 emissions are combined with an atmospheric dispersion model to create pseudo-observations. Clean air from the North Atlantic passed over mainland UK, picking up anthropogenic emissions. To best explain the observed plume using pseudo-observations, an additional North Sea source from the gas rigs area is added. Third, the δ13C-CH4 from the plume is shown to be -53‰, which is lighter than fossil gas but heavier than the UK average emission. We conclude that either an additional small-area mainland source is needed, combined with temporal variability in emission or transport in small-scale meteorological features. Alternatively, a combination of additional sources that are at least 75% from the mainland (-58‰) and up to 25% from the North Sea gas rigs area (-32‰) would explain the measurements. Had the isotopic analysis not been performed, the likely conclusion would have been of a gas field source of CH4. This demonstrates the limitation of analyzing mole fractions alone, as the simplest explanation is rejected based on analysis of isotopic data.

Context influences on TALE–DNA binding revealed by quantitative profiling

PubMed Central

Rogers, Julia M.; Barrera, Luis A.; Reyon, Deepak; Sander, Jeffry D.; Kellis, Manolis; Joung, J Keith; Bulyk, Martha L.

2015-01-01

Transcription activator-like effector (TALE) proteins recognize DNA using a seemingly simple DNA-binding code, which makes them attractive for use in genome engineering technologies that require precise targeting. Although this code is used successfully to design TALEs to target specific sequences, off-target binding has been observed and is difficult to predict. Here we explore TALE–DNA interactions comprehensively by quantitatively assaying the DNA-binding specificities of 21 representative TALEs to ∼5,000–20,000 unique DNA sequences per protein using custom-designed protein-binding microarrays (PBMs). We find that protein context features exert significant influences on binding. Thus, the canonical recognition code does not fully capture the complexity of TALE–DNA binding. We used the PBM data to develop a computational model, Specificity Inference For TAL-Effector Design (SIFTED), to predict the DNA-binding specificity of any TALE. We provide SIFTED as a publicly available web tool that predicts potential genomic off-target sites for improved TALE design. PMID:26067805

Deterioration of glycemic control after corticosteroid administration in islet autotransplant recipients: a cautionary tale.

PubMed

Ngo, Anh; Sutherland, David E R; Beilman, Gregory J; Bellin, Melena D

2014-02-01

Islet autotransplantation (IAT) is performed at the time of total pancreatectomy (TP) to prevent or minimize post-surgical diabetes. Corticosteroids induce insulin resistance and present a risk to islet autografts, through glucotoxicity and increased metabolic demand on a marginal islet mass. We present four IAT recipients treated with oral or injected corticosteroids after transplant for medical conditions unrelated to chronic pancreatitis or TPIAT. Hyperglycemia or insulin resistance was evident in all four patients, including reversion to long-term insulin therapy in two patients. One patient receiving corticosteroid injections had a transient increase in hemoglobin A1c (+0.6% above baseline), and one patient given a one time dose of oral dexamethasone exhibited hyperglycemia despite high insulin (>200 mU/L) and C-peptide (15.3 ng/mL) production on an oral glucose tolerance test. IAT recipients have insufficient islet mass to compensate for the insulin resistance induced by corticosteroids. Caution should be given to using these agents in IAT recipients. When corticosteroids are medically necessary, insulin therapy should be administered temporarily to compensate for the increased metabolic demand and minimize long-term risks on the islet graft.

The Infectious Diseases Society of America Lyme guidelines: a cautionary tale about the development of clinical practice guidelines

PubMed Central

2010-01-01

Flawed clinical practice guidelines may compromise patient care. Commercial conflicts of interest on panels that write treatment guidelines are particularly problematic, because panelists may have conflicting agendas that influence guideline recommendations. Historically, there has been no legal remedy for conflicts of interest on guidelines panels. However, in May 2008, the Attorney General of Connecticut concluded a ground-breaking antitrust investigation into the development of Lyme disease treatment guidelines by one of the largest medical societies in the United States, the Infectious Diseases Society of America (IDSA). Although the investigation found significant flaws in the IDSA guidelines development process, the subsequent review of the guidelines mandated by the settlement was compromised by a lack of impartiality at various stages of the IDSA review process. This article will examine the interplay between the recent calls for guidelines reform, the ethical canons of medicine, and due process considerations under antitrust laws as they apply to the formulation of the IDSA Lyme disease treatment guidelines. The article will also discuss pitfalls in the implementation of the IDSA antitrust settlement that should be avoided in the future. PMID:20529367

Assessing ExxonMobil's Climate Change Communications (1977-2014)

NASA Astrophysics Data System (ADS)

Supran, G.; Oreskes, N.

2017-12-01

Coal, oil, and gas companies have operated - and continue to operate - across myriad facets of the climate problem: scientific, political, and public. Efforts to engage the fossil fuel industry in addressing climate change should therefore be informed by this broad historical context. In this paper, we present an empirical document-by-document textual content analysis and comparison of 187 diverse climate change communications from ExxonMobil spanning 1977 to 2014, including peer-reviewed and non-peer-reviewed publications, internal company documents, and paid, editorial-style advertisements ("advertorials") in The New York Times. We examine whether these communications sent consistent messages about the state of climate science and its implications - specifically, we compare their positions on climate change as real, human-caused, serious, and solvable. In all four cases, we find that as documents become more publicly accessible, they increasingly communicate doubt. That is, ExxonMobil contributed to advancing climate science - by way of its scientists' academic publications - but promoted doubt about it in advertorials. Our findings shed light on one oil and gas company's multivalent strategic responses to climate change. They offer a cautionary tale against myopic engagement with the fossil fuel industry, demonstrating the importance of evaluating the full spectrum of a company's claims and activities.

Colorectal cancer biomarkers: To be or not to be? Cautionary tales from a road well travelled

PubMed Central

Fung, Kim YC; Nice, Edouard; Priebe, Ilka; Belobrajdic, Damien; Phatak, Aloke; Purins, Leanne; Tabor, Bruce; Pompeia, Celine; Lockett, Trevor; Adams, Timothy E; Burgess, Antony; Cosgrove, Leah

2014-01-01

Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide and places a major economic burden on the global health care system. The time frame for development from premalignant to malignant disease typically spans 10-15 years, and this latent period provides an ideal opportunity for early detection and intervention to improve patient outcomes. Currently, early diagnosis of CRC is hampered by a lack of suitable non-invasive biomarkers that are clinically or economically acceptable for population-based screening. New blood-based protein biomarkers for early detection of CRC are therefore urgently required. The success of clinical biomarker discovery and validation studies is critically dependent on understanding and adjusting for potential experimental, analytical, and biological factors that can interfere with the robust interpretation of results. In this review we outline some important considerations for research groups undertaking biomarker research with exemplars from our studies. Implementation of experimental strategies to minimise the potential effects of these problems will facilitate the identification of panels of biomarkers with the sensitivity and specificity required for the development of successful tests for the early detection and surveillance of CRC. PMID:24574763

Health sector reform in Argentina: a cautionary tale.

PubMed

Lloyd-Sherlock, Peter

2005-04-01

In November 2002 the World Bank published a report on the Argentine health sector. The report accurately portrays the complexity and severity of the problems facing the health care system. It stresses that these problems are not purely a product of the country's economic collapse, noting that the system has suffered from long-standing structural problems and inefficiencies. Curiously, the report makes no mention of the leading role played by the World Bank in health reform efforts during the 1990s. This paper demonstrates that these reforms did much to worsen pre-existing weaknesses of the sector. The paper criticises the content of the reform agenda and the manner in which it was produced, arguing that these were reforms in which considerations of public health were less significant than conformity to the wider model of neo-liberal social and economic development prevailing at the time. It also highlights problems of implementing the reform agenda, which reduced the coherency of the reforms. The paper goes on to examine the impact of the crisis, noting links with the preceding reforms. It identifies a number of insights and lessons of potential value to other countries which are pursuing similar policies.

The importance of multilocus sequence typing: cautionary tales from the bacterium Xylella fastidiosa.

PubMed

Nunney, L; Elfekih, S; Stouthamer, R

2012-05-01

Microbial identification methods have evolved rapidly over the last few decades. One such method is multilocus sequence typing (MLST). MLST is a powerful tool for understanding the evolutionary dynamics of pathogens and to gain insight into their genetic diversity. We illustrate the importance of accurate typing by reporting on three problems that have arisen in the study of a single bacterial species, the plant pathogen Xylella fastidiosa. Two of these were particularly serious since they concerned contamination of important research material that has had detrimental consequences for Xylella research: the contamination of DNA used in the sequencing of an X. fastidiosa genome (Ann-1) with DNA from another X. fastidiosa strain, and the unrecognized mislabeling of a strain (Temecula1) distributed from a culture collection (ATCC). We advocate the routine use of MLST to define strains maintained in culture collections and emphasize the importance of confirming the purity of DNA submitted for sequencing. We also present a third example that illustrates the value of MLST in guiding the choice of taxonomic types. Beyond these situations, there is a strong case for MLST whenever an isolate is used experimentally, especially where genotypic differences are suspected to influence the outcome.

'Taking charge of your health': discourses of responsibility in English-Canadian women's magazines.

PubMed

Roy, Stephannie C

2008-04-01

This article presents an examination of the ways in which responsibility for health is constructed in popular English-Canadian women's magazines. Women's magazines are a unique media form, acting as guidebooks for women on matters relating to feminine gender roles and are important to examine as part of the corpus of societal discourses which frame our understandings of what it means to be healthy and how good health is achieved. Using discourse analysis several techniques were found which reinforce women's individual responsibility to create and maintain good health for themselves and their families. The magazines instruct women/readers directly about their health-related responsibilities and outline the negative consequences of inaction or incorrect action. The magazines also use the traditional discursive technique of women's personal accounts as both cautionary tales and inspirational stories to encourage readers to actively pursue healthy behaviours. Reflecting and reinforcing the discourse of healthism, women's magazines consistently present health as an important individual responsibility and a moral imperative which creates an entrepreneurial subject position for women. The article concludes by discussing the implications for women's magazine audiences within the ongoing feminist debate about this cultural industry.

Semicircular Canal Size and Locomotion in Colobine Monkeys: A Cautionary Tale.

PubMed

Rae, Todd C; Johnson, Paul Martin; Yano, Wataru; Hirasaki, Eishi

2016-01-01

The semicircular canals of the inner ear constitute the organ of balance, tracking head rotation during movement and facilitating stabilisation of vision. Morphological characteristics of the canals are correlated with agility scores related to locomotion. To date, however, the relationship between canal morphology and specific locomotor behaviours, such as leaping, is unclear. Knowledge of such a relationship could strengthen the inferences of locomotion of extinct taxa. To test this, crania of two sets of closely related primate species (Presbytis melalophos and P. potenziani; Colobus guereza and C. polykomos) that differ in the percentage of leaping in their locomotor repertoire were examined using microscopic computed tomography. Three-dimensional virtual models of the bony labyrinth were derived, and the radius of curvature of each of the three canals was evaluated relative to cranial size. The findings are contradictory; one leaping form (P. melalophos) differs from its congener in possessing significantly larger lateral canals, a pattern seen in previous studies of primates, while the other leaper (C. guereza) has significantly smaller posterior canals than its close relative. These results undermine efforts to determine specific locomotor behaviours from the bony labyrinth of extinct primates. © 2016 S. Karger AG, Basel.

Endotoxin Contamination of Apolipoprotein A-I: Effect on Macrophage Proliferation – A Cautionary Tale

PubMed Central

Jin, Xueting; Xu, Qing; Champion, Keith; Kruth, Howard S.

2015-01-01

This technical report addresses the problem of endotoxin contamination of apolipoprotein reagents. Using a bromodeoxyuridine incorporation cell proliferation assay, we observed that human plasma ApoA-I as low as 1 μg/ml resulted in a >90% inhibition in macrophage proliferation. However, not all ApoA-I from different sources showed this effect. We considered the possibility that endotoxin contamination of the apolipoproteins contributed to the differential inhibition of macrophage cell proliferation. Endotoxin alone very potently inhibited macrophage proliferation (0.1 ng/ml inhibited macrophage proliferation >90%). Measurement of endotoxin levels in the apolipoprotein products, including an analysis of free versus total endotoxin, the latter which included endotoxin that was masked due to binding to protein, suggested that free endotoxin mediated inhibition of macrophage proliferation. Despite the use of an advanced endotoxin removal procedure and agents commonly used to inhibit endotoxin action, the potency of endotoxin precluded successful elimination of endotoxin effect. Our findings show that endotoxin contamination can significantly influence apparent apolipoprotein-mediated cell effects (or effects of any other biological products), especially when these products are tested on highly endotoxin-sensitive cells, such as macrophages. PMID:25778625

Endotoxin contamination of apolipoprotein A-I: effect on macrophage proliferation--a cautionary tale.

PubMed

Jin, Xueting; Xu, Qing; Champion, Keith; Kruth, Howard S

2015-05-01

This technical report addresses the problem of endotoxin contamination of apolipoprotein reagents. Using a bromodeoxyuridine incorporation cell proliferation assay, we observed that human plasma ApoA-I as low as 1 μg/ml resulted in a >90% inhibition in macrophage proliferation. However, not all ApoA-I from different sources showed this effect. We considered the possibility that endotoxin contamination of the apolipoproteins contributed to the differential inhibition of macrophage cell proliferation. Endotoxin alone very potently inhibited macrophage proliferation (0.1 ng/ml inhibited macrophage proliferation>90%). Measurement of endotoxin levels in the apolipoprotein products, including an analysis of free versus total endotoxin, the latter which included endotoxin that was masked due to binding to protein, suggested that free endotoxin mediated inhibition of macrophage proliferation. Despite the use of an advanced endotoxin removal procedure and agents commonly used to inhibit endotoxin action, the potency of endotoxin precluded successful elimination of endotoxin effect. Our findings show that endotoxin contamination can significantly influence apparent apolipoprotein-mediated cell effects (or effects of any other biological products), especially when these products are tested on highly endotoxin-sensitive cells, such as macrophages. Published by Elsevier Ireland Ltd.

Curricular Policy as a Collective Effects Problem: A Distributional Approach

PubMed Central

Penner, Andrew M.; Domina, Thurston; Penner, Emily K.; Conley, AnneMarie

2015-01-01

Current educational policies in the United States attempt to boost student achievement and promote equality by intensifying the curriculum and exposing students to more advanced coursework. This paper investigates the relationship between one such effort -- California's push to enroll all 8th grade students in Algebra -- and the distribution of student achievement. We suggest that this effort is an instance of a “collective effects” problem, where the population-level effects of a policy are different from its effects at the individual level. In such contexts, we argue that it is important to consider broader population effects as well as the difference between “treated” and “untreated” individuals. To do so, we present differences in inverse propensity score weighted distributions to investigate how this curricular policy changed the distribution of student achievement more broadly. We find that California's attempt to intensify the curriculum did not raise test scores at the bottom of the distribution, but did lower scores at the top of the distribution. These results highlight the efficacy of inverse propensity score weighting approaches for estimating collective effects, and provide a cautionary tale for curricular intensification efforts and other policies with collective effects. PMID:26004485

Cochlear implantation in children with Jervell and Lange-Nielsen syndrome - a cautionary tale.

PubMed

Broomfield, Stephen J; Bruce, Iain A; Henderson, Lise; Ramsden, Richard T; Green, Kevin M J

2012-08-01

Jervell and Lange-Nielsen (JLN) syndrome is a rare cause of congenital profound hearing loss associated with a prolonged QT interval on the electrocardiogram. Children presenting for cochlear implantation with this condition may be asymptomatic but are at risk of sudden death. SCREENING AND SUBSEQUENT: careful management is therefore required to ensure a successful outcome. We present our experience of cochlear implantation in children with JLN syndrome, including two who died unexpectedly, and suggest a protocol for management of such cases. Clinical presentation Four cases of cochlear implantation in JLN syndrome are described. None had any previous cardiological family history. Two were diagnosed pre-operatively but, despite appropriate management under a cardiologist, died from cardiac arrest; the first in the perioperative period following reimplantation for infection, and the second unrelated to his cochlear implant surgery. The other two patients were diagnosed only subsequent to their implantation and continue to use their implants successfully. These cases highlight the variation in presentation of JLN syndrome, and the spectrum of disease severity that exists. Our protocol stresses the importance of careful assessment and counselling of parents by an experienced implant team.

Characterization of TALE genes expression during the first lineage segregation in mammalian embryos.

PubMed

Sonnet, Wendy; Rezsöhazy, Rene; Donnay, Isabelle

2012-11-01

Three amino acid loop extension (TALE) homeodomain-containing transcription factors are generally recognized for their role in organogenesis and differentiation during embryogenesis. However, very little is known about the expression and function of Meis, Pbx, and Prep genes during early development. In order to determine whether TALE proteins could contribute to the early cell fate decisions in mammalian development, this study aimed to characterize in a systematic manner the pattern of expression of all Meis, Pbx, and Prep genes from the precompaction to blastocyst stage corresponding to the first step of cell differentiation in mammals. To reveal to what extent TALE genes expression at these early stages is a conserved feature among mammals, this study was performed in parallel in the bovine and mouse models. We demonstrated the transcription and translation of TALE genes, before gastrulation in the two species. At least one member of Meis, Pbx, and Prep subfamilies was found expressed at the RNA and protein levels but different patterns of expression were observed between genes and between species, suggesting specific gene regulations. Taken together, these results suggest a previously unexpected involvement of these factors during the early development in mammals. Copyright © 2012 Wiley Periodicals, Inc.

31 CFR Appendix A to Part 501 - Economic Sanctions Enforcement Guidelines.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., structure or arrangement that was designed or implemented with the intent to prevent or shield the Subject..., findings of violations or cautionary, warning or evaluative letters, or other administrative actions... action taken with respect to the Subject Person, including any cautionary, warning or evaluative letters...

31 CFR Appendix A to Part 501 - Economic Sanctions Enforcement Guidelines.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., structure or arrangement that was designed or implemented with the intent to prevent or shield the Subject..., findings of violations or cautionary, warning or evaluative letters, or other administrative actions... action taken with respect to the Subject Person, including any cautionary, warning or evaluative letters...

31 CFR Appendix A to Part 501 - Economic Sanctions Enforcement Guidelines.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., structure or arrangement that was designed or implemented with the intent to prevent or shield the Subject..., findings of violations or cautionary, warning or evaluative letters, or other administrative actions... action taken with respect to the Subject Person, including any cautionary, warning or evaluative letters...

31 CFR Appendix A to Part 501 - Economic Sanctions Enforcement Guidelines.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., structure or arrangement that was designed or implemented with the intent to prevent or shield the Subject..., findings of violations or cautionary, warning or evaluative letters, or other administrative actions... action taken with respect to the Subject Person, including any cautionary, warning or evaluative letters...

Conformational elasticity can facilitate TALE-DNA recognition

PubMed Central

Lei, Hongxing; Sun, Jiya; Baldwin, Enoch P.; Segal, David J.; Duan, Yong

2015-01-01

Sequence-programmable transcription activator-like effector (TALE) proteins have emerged as a highly efficient tool for genome engineering. Recent crystal structures depict a transition between an open unbound solenoid and more compact DNA-bound solenoid formed by the 34 amino acid repeats. How TALEs switch conformation between these two forms without substantial energetic compensation, and how the repeat-variable di-residues (RVDs) discriminate between the cognate base and other bases still remain unclear. Computational analysis on these two aspects of TALE-DNA interaction mechanism has been conducted in order to achieve a better understanding of the energetics. High elasticity was observed in the molecular dynamics simulations of DNA-free TALE structure that started from the bound conformation where it sampled a wide range of conformations including the experimentally determined apo- and bound- conformations. This elastic feature was also observed in the simulations starting from the apo form which suggests low free energy barrier between the two conformations and small compensation required upon binding. To analyze binding specificity, we performed free energy calculations of various combinations of RVDs and bases using Poisson-Boltzmann/surface area (PBSA) and other approaches. The PBSA calculations indicated that the native RVD-base structures had lower binding free energy than mismatched structures for most of the RVDs examined. Our theoretical analyses provided new insight on the dynamics and energetics of TALE-DNA binding mechanism. PMID:24629191

Conformational elasticity can facilitate TALE-DNA recognition.

PubMed

Lei, Hongxing; Sun, Jiya; Baldwin, Enoch P; Segal, David J; Duan, Yong

2014-01-01

Sequence-programmable transcription activator-like effector (TALE) proteins have emerged as a highly efficient tool for genome engineering. Recent crystal structures depict a transition between an open unbound solenoid and more compact DNA-bound solenoid formed by the 34 amino acid repeats. How TALEs switch conformation between these two forms without substantial energetic compensation, and how the repeat-variable di-residues (RVDs) discriminate between the cognate base and other bases still remain unclear. Computational analysis on these two aspects of TALE-DNA interaction mechanism has been conducted in order to achieve a better understanding of the energetics. High elasticity was observed in the molecular dynamics simulations of DNA-free TALE structure that started from the bound conformation where it sampled a wide range of conformations including the experimentally determined apo and bound conformations. This elastic feature was also observed in the simulations starting from the apo form which suggests low free energy barrier between the two conformations and small compensation required upon binding. To analyze binding specificity, we performed free energy calculations of various combinations of RVDs and bases using Poisson-Boltzmann surface area (PBSA) and other approaches. The PBSA calculations indicated that the native RVD-base structures had lower binding free energy than mismatched structures for most of the RVDs examined. Our theoretical analyses provided new insight on the dynamics and energetics of TALE-DNA binding mechanism. © 2014 Elsevier Inc. All rights reserved.

Report on the Selection Procedure Based on Readers' Responses to the Original Nine Tales in Turkey. Fairytale: An Interdisciplinary Turco-Danish Study of the Collective v. the Individual Nature of the Response to Literature. Report No. 9. Revised.

ERIC Educational Resources Information Center

Doltas, Dilek, Ed.; And Others

Prepared as part of the Turko-Danish Fairytale Project conducted to uncover universal, cross-cultural features in readers' response to literature, this paper reports on a pilot study to determine which three out of nine preselected fairy tales would elicit the most faceted response from a population of Turkish readers. After explaining the…

A TALE of transposition: Tn3-like transposons play a major role in the spread of pathogenicity determinants of Xanthomonas citri and other xanthomonads.

PubMed

Ferreira, Rafael Marini; de Oliveira, Amanda Carolina P; Moreira, Leandro M; Belasque, José; Gourbeyre, Edith; Siguier, Patricia; Ferro, Maria Inês T; Ferro, Jesus A; Chandler, Michael; Varani, Alessandro M

2015-02-17

Members of the genus Xanthomonas are among the most important phytopathogens. A key feature of Xanthomonas pathogenesis is the translocation of type III secretion system (T3SS) effector proteins (T3SEs) into the plant target cells via a T3SS. Several T3SEs and a murein lytic transglycosylase gene (mlt, required for citrus canker symptoms) are found associated with three transposition-related genes in Xanthomonas citri plasmid pXAC64. These are flanked by short inverted repeats (IRs). The region was identified as a transposon, TnXax1, with typical Tn3 family features, including a transposase and two recombination genes. Two 14-bp palindromic sequences within a 193-bp potential resolution site occur between the recombination genes. Additional derivatives carrying different T3SEs and other passenger genes occur in different Xanthomonas species. The T3SEs include transcription activator-like effectors (TALEs). Certain TALEs are flanked by the same IRs as found in TnXax1 to form mobile insertion cassettes (MICs), suggesting that they may be transmitted horizontally. A significant number of MICs carrying other passenger genes (including a number of TALE genes) were also identified, flanked by the same TnXax1 IRs and delimited by 5-bp target site duplications. We conclude that a large fraction of T3SEs, including individual TALEs and potential pathogenicity determinants, have spread by transposition and that TnXax1, which exhibits all of the essential characteristics of a functional transposon, may be involved in driving MIC transposition. We also propose that TALE genes may diversify by fork slippage during the replicative Tn3 family transposition. These mechanisms may play a crucial role in the emergence of Xanthomonas pathogenicity. Xanthomonas genomes carry many insertion sequences (IS) and transposons, which play an important role in their evolution and architecture. This study reveals a key relationship between transposons and pathogenicity determinants in Xanthomonas. We propose that several transposition events mediated by a Tn3-like element carrying different sets of passenger genes, such as different type III secretion system effectors (including transcription activation-like effectors [TALEs]), were determinant in the evolution and emergence of Xanthomonas pathogenicity. TALE genes are DNA-binding effectors that modulate plant transcription. We also present a model for generating TALE gene diversity based on fork slippage associated with the replicative transposition mechanism of Tn3-like transposons. This may provide a mechanism for niche adaptation, specialization, host-switching, and other lifestyle changes. These results will also certainly lead to novel insights into the evolution and emergence of the various diseases caused by different Xanthomonas species and pathovars. Copyright © 2015 Marini Ferreira et al.

Cautionary Note on Reporting Eta-Squared Values from Multifactor ANOVA Designs

ERIC Educational Resources Information Center

Pierce, Charles A.; Block, Richard A.; Aguinis, Herman

2004-01-01

The authors provide a cautionary note on reporting accurate eta-squared values from multifactor analysis of variance (ANOVA) designs. They reinforce the distinction between classical and partial eta-squared as measures of strength of association. They provide examples from articles published in premier psychology journals in which the authors…

Revisiting the NMR structure of the ultrafast downhill folding protein gpW from bacteriophage λ.

PubMed

Sborgi, Lorenzo; Verma, Abhinav; Muñoz, Victor; de Alba, Eva

2011-01-01

GpW is a 68-residue protein from bacteriophage λ that participates in virus head morphogenesis. Previous NMR studies revealed a novel α+β fold for this protein. Recent experiments have shown that gpW folds in microseconds by crossing a marginal free energy barrier (i.e., downhill folding). These features make gpW a highly desirable target for further experimental and computational folding studies. As a step in that direction, we have re-determined the high-resolution structure of gpW by multidimensional NMR on a construct that eliminates the purification tags and unstructured C-terminal tail present in the prior study. In contrast to the previous work, we have obtained a full manual assignment and calculated the structure using only unambiguous distance restraints. This new structure confirms the α+β topology, but reveals important differences in tertiary packing. Namely, the two α-helices are rotated along their main axis to form a leucine zipper. The β-hairpin is orthogonal to the helical interface rather than parallel, displaying most tertiary contacts through strand 1. There also are differences in secondary structure: longer and less curved helices and a hairpin that now shows the typical right-hand twist. Molecular dynamics simulations starting from both gpW structures, and calculations with CS-Rosetta, all converge to our gpW structure. This confirms that the original structure has strange tertiary packing and strained secondary structure. A comparison of NMR datasets suggests that the problems were mainly caused by incomplete chemical shift assignments, mistakes in NOE assignment and the inclusion of ambiguous distance restraints during the automated procedure used in the original study. The new gpW corrects these problems, providing the appropriate structural reference for future work. Furthermore, our results are a cautionary tale against the inclusion of ambiguous experimental information in the determination of protein structures.

New genetic and morphological evidence suggests a single hoaxer created `Piltdown man'

NASA Astrophysics Data System (ADS)

De Groote, Isabelle; Flink, Linus Girdland; Abbas, Rizwaan; Bello, Silvia M.; Burgia, Lucia; Buck, Laura Tabitha; Dean, Christopher; Freyne, Alison; Higham, Thomas; Jones, Chris G.; Kruszynski, Robert; Lister, Adrian; Parfitt, Simon A.; Skinner, Matthew M.; Shindler, Karolyn; Stringer, Chris B.

2016-08-01

In 1912, palaeontologist Arthur Smith Woodward and amateur antiquarian and solicitor Charles Dawson announced the discovery of a fossil that supposedly provided a link between apes and humans: Eoanthropus dawsoni (Dawson's dawn man). The publication generated huge interest from scientists and the general public. However, `Piltdown man's' initial celebrity has long been overshadowed by its subsequent infamy as one of the most famous scientific frauds in history. Our re-evaluation of the Piltdown fossils using the latest scientific methods (DNA analyses, high-precision measurements, spectroscopy and virtual anthropology) shows that it is highly likely that a single orang-utan specimen and at least two human specimens were used to create the fake fossils. The modus operandi was found consistent throughout the assemblage (specimens are stained brown, loaded with gravel fragments and restored using filling materials), linking all specimens from the Piltdown I and Piltdown II sites to a single forger-Charles Dawson. Whether Dawson acted alone is uncertain, but his hunger for acclaim may have driven him to risk his reputation and misdirect the course of anthropology for decades. The Piltdown hoax stands as a cautionary tale to scientists not to be led by preconceived ideas, but to use scientific integrity and rigour in the face of novel discoveries.

Tsunamis in the geological record: Making waves with a cautionary tale from the Mediterranean

PubMed Central

Marriner, Nick; Kaniewski, David; Morhange, Christophe; Flaux, Clément; Giaime, Matthieu; Vacchi, Matteo; Goff, James

2017-01-01

From 2000 to 2015, tsunamis and storms killed more than 430,000 people worldwide and affected a further >530 million, with total damages exceeding US$970 billion. These alarming trends, underscored by the tragic events of the 2004 Indian Ocean catastrophe, have fueled increased worldwide demands for assessments of past, present, and future coastal risks. Nonetheless, despite its importance for hazard mitigation, discriminating between storm and tsunami deposits in the geological record is one of the most challenging and hotly contended topics in coastal geoscience. To probe this knowledge gap, we present a 4500-year reconstruction of “tsunami” variability from the Mediterranean based on stratigraphic but not historical archives and assess it in relation to climate records and reconstructions of storminess. We elucidate evidence for previously unrecognized “tsunami megacycles” with three peaks centered on the Little Ice Age, 1600, and 3100 cal. yr B.P. (calibrated years before present). These ~1500-year cycles, strongly correlated with climate deterioration in the Mediterranean/North Atlantic, challenge up to 90% of the original tsunami attributions and suggest, by contrast, that most events are better ascribed to periods of heightened storminess. This timely and provocative finding is crucial in providing appropriately tailored assessments of coastal hazard risk in the Mediterranean and beyond. PMID:29026879

Researching Together: A CTSA Partnership of Academicians and Communities for Translation

PubMed Central

Nearing, Kathryn; Felzien, Maret; Green, Larry; Calonge, Ned; Pineda‐Reyes, Fernando; Jones, Grant; Tamez, Montelle; Miller, Sara; Kramer, Andrew

2013-01-01

Abstract Background The Colorado Clinical and Translational Sciences Institute (CCTSI) aims to translate discovery into clinical practice. The Partnership of Academicians and Communities for Translation (PACT) represents a robust campus–community partnership. Methods The CCTSI collected data on all PACT activities including meeting notes, staff activity logs, stakeholder surveys and interviews, and several key component in‐depth evaluations. Data analysis by Evaluation and Community Engagement Core and PACT Council members identified critical shifts that changed the trajectory of community engagement efforts. Results Ten “critical shifts” in six broad rubrics created change in the PACT. Critical shifts were decision points in the development of the PACT that represented quantitative and qualitative changes in the work and trajectory. Critical shifts occurred in PACT management and leadership, financial control and resource allocation, and membership and voice. Discussion The development of a campus–community partnership is not a smooth linear path. Incremental changes lead to major decision points that represent an opportunity for critical shifts in developmental trajectory. We provide an enlightening, yet cautionary, tale to others considering a campus–community partnership so they may prepare for crucial decisions and critical shifts. The PACT serves as a genuine foundational platform for dynamic research efforts aimed at eliminating health disparities. PMID:24127922

Tsunamis in the geological record: Making waves with a cautionary tale from the Mediterranean.

PubMed

Marriner, Nick; Kaniewski, David; Morhange, Christophe; Flaux, Clément; Giaime, Matthieu; Vacchi, Matteo; Goff, James

2017-10-01

From 2000 to 2015, tsunamis and storms killed more than 430,000 people worldwide and affected a further >530 million, with total damages exceeding US$970 billion. These alarming trends, underscored by the tragic events of the 2004 Indian Ocean catastrophe, have fueled increased worldwide demands for assessments of past, present, and future coastal risks. Nonetheless, despite its importance for hazard mitigation, discriminating between storm and tsunami deposits in the geological record is one of the most challenging and hotly contended topics in coastal geoscience. To probe this knowledge gap, we present a 4500-year reconstruction of "tsunami" variability from the Mediterranean based on stratigraphic but not historical archives and assess it in relation to climate records and reconstructions of storminess. We elucidate evidence for previously unrecognized "tsunami megacycles" with three peaks centered on the Little Ice Age, 1600, and 3100 cal. yr B.P. (calibrated years before present). These ~1500-year cycles, strongly correlated with climate deterioration in the Mediterranean/North Atlantic, challenge up to 90% of the original tsunami attributions and suggest, by contrast, that most events are better ascribed to periods of heightened storminess. This timely and provocative finding is crucial in providing appropriately tailored assessments of coastal hazard risk in the Mediterranean and beyond.

Ethnographic critique and technoscientific narratives: the old mole, ethical plateaux, and the governance of emergent biosocial polities.

PubMed

Fischer, M M

2001-12-01

A reading of the puzzle novel Vienna Blood, by Adrian Mathews, is juxtaposed to three ethnographic sketches of contemporary ethical plateaus or domains of ethical challenge--the challenges of informed public consent to new technologies, the seductions to do whatever is medically possible (sometimes at the expense of quality of life or the good death'). and the power of money in driving the biotechnological industries. Vienna Blood deals with precautionary germplasm modification and chemical camouflage justified as protection against ethnically-targeted biological warfare, and touches on a series of technologies such as new reproductive technologies, genetic engineering, and cryptographic attacks and defenses, as well as the ability to evade regulatory controls. Such technoscientifically informed novels are useful as cautionary tales, in exploring the complexity and interaction among new technologies, and the phantasmagoria that help drive new technologies. They are not so good at thinking through institutional development: a challenge for ethnography and new social theory. Ethnography, like novels, can function as checks on the mechanisms of abstraction and universalization that frequently bedevil the non-anthropological, non-cross-culturally or cross-temporally comparative, social sciences. Questions are raised about new or emergent biosocialities, forms of governance, and forms of cultural critique.

The effects of incubation temperature on the development of the cortical forebrain in a lizard.

PubMed

Amiel, Joshua J; Bao, Shisan; Shine, Richard

2017-01-01

The embryos of egg-laying species are exposed to variable thermal regimes, which can influence not only the resultant hatchling's morphology (e.g., size, sex) and performance (e.g., locomotor speed), but also its cognitive performance (learning ability). To clarify the proximate basis for this latter effect, we incubated eggs of the scincid lizard Bassiana duperreyi under simulated 'hot' and 'cold' natural nest temperatures to examine the effect of incubation temperature on the structure of the telencephalon region of the forebrain. Hatchlings from low-temperature incubation had larger telencephalons (both in absolute terms and relative to body size) and larger neurons in their medial cortices, whereas the medial cortices of hatchlings from high-temperature incubation had fewer neurons overall, but greater neuronal density, and more neurons in certain areas. These temperature-induced differences in B. duperreyi forebrain development are consistent with (and may explain) the disparities in learning ability between hatchlings from our two incubation treatments. The phenotypic plasticity of lizard telencephalon anatomy in response to incubation temperature presents exciting opportunities for studies on the evolutionary and developmental determinants of intelligence in vertebrates, but also offers a cautionary tale. Global climate changes, wrought by anthropogenic activities, may directly modify brain structure in reptiles.

New genetic and morphological evidence suggests a single hoaxer created 'Piltdown man'.

PubMed

De Groote, Isabelle; Flink, Linus Girdland; Abbas, Rizwaan; Bello, Silvia M; Burgia, Lucia; Buck, Laura Tabitha; Dean, Christopher; Freyne, Alison; Higham, Thomas; Jones, Chris G; Kruszynski, Robert; Lister, Adrian; Parfitt, Simon A; Skinner, Matthew M; Shindler, Karolyn; Stringer, Chris B

2016-08-01

In 1912, palaeontologist Arthur Smith Woodward and amateur antiquarian and solicitor Charles Dawson announced the discovery of a fossil that supposedly provided a link between apes and humans: Eoanthropus dawsoni (Dawson's dawn man). The publication generated huge interest from scientists and the general public. However, 'Piltdown man's' initial celebrity has long been overshadowed by its subsequent infamy as one of the most famous scientific frauds in history. Our re-evaluation of the Piltdown fossils using the latest scientific methods (DNA analyses, high-precision measurements, spectroscopy and virtual anthropology) shows that it is highly likely that a single orang-utan specimen and at least two human specimens were used to create the fake fossils. The modus operandi was found consistent throughout the assemblage (specimens are stained brown, loaded with gravel fragments and restored using filling materials), linking all specimens from the Piltdown I and Piltdown II sites to a single forger-Charles Dawson. Whether Dawson acted alone is uncertain, but his hunger for acclaim may have driven him to risk his reputation and misdirect the course of anthropology for decades. The Piltdown hoax stands as a cautionary tale to scientists not to be led by preconceived ideas, but to use scientific integrity and rigour in the face of novel discoveries.

Exploring the Cautionary Attitude toward Wikipedia in Higher Education: Implications for Higher Education Institutions

ERIC Educational Resources Information Center

Bayliss, Gemma

2013-01-01

This article presents the research findings of a small-scale study which aimed to explore the cautionary attitude toward the use of Wikipedia in the process of learning. A qualitative case study approach was taken, using literature review, institutional documentation, and semi-structured interviews with five members of academic teaching staff from…

XA23 is an executor R protein and confers broad-spectrum disease resistance in rice.

PubMed

Wang, Chunlian; Zhang, Xiaoping; Fan, Yinglun; Gao, Ying; Zhu, Qinlong; Zheng, Chongke; Qin, Tengfei; Li, Yanqiang; Che, Jinying; Zhang, Mingwei; Yang, Bing; Liu, Yaoguang; Zhao, Kaijun

2015-02-01

The majority of plant disease resistance (R) genes encode proteins that share common structural features. However, the transcription activator-like effector (TALE)-associated executor type R genes show no considerable sequence homology to any known R genes. We adopted a map-based cloning approach and TALE-based technology to isolate and characterize Xa23, a new executor R gene derived from wild rice (Oryza rufipogon) that confers an extremely broad spectrum of resistance to bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo). Xa23 encodes a 113 amino acid protein that shares 50% identity with the known executor R protein XA10. The predicted transmembrane helices in XA23 also overlap with those of XA10. Unlike Xa10, however, Xa23 transcription is specifically activated by AvrXa23, a TALE present in all examined Xoo field isolates. Moreover, the susceptible xa23 allele has an identical open reading frame of Xa23 but differs in promoter region by lacking the TALE binding element (EBE) for AvrXa23. XA23 can trigger a strong hypersensitive response in rice, tobacco, and tomato. Our results provide the first evidence that plant genomes have an executor R gene family of which members execute their function and spectrum of disease resistance by recognizing the cognate TALEs in the pathogen. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

Perceptions and Knowledge of Caffeinated Energy Drinks: Results of Focus Groups With Canadian Youth.

PubMed

McCrory, Cassondra; White, Christine M; Bowman, Carolyn; Fenton, Nancy; Reid, Jessica L; Hammond, David

2017-04-01

To examine use, knowledge, and perceptions of caffeinated energy drinks (CEDs) among youth. Qualitative research using focus group discussions (n = 4). Two Canadian cities (Toronto and Montreal). Youth aged 12-18 years (n = 41). Perceived definitions of CEDs, reasons for use, knowledge of health effects, use with alcohol, marketing perceptions, and use and understanding of cautionary statements on packaging. Data were analyzed using a modified grounded-theory approach. Youth identified CEDs as products that provide energy and contain caffeine and sugar. Compared with mainstream CED brands and energy shots, youth were less likely to perceive Gatorade, Coca-Cola, and a Starbucks beverage as energy drinks, despite some ambiguity. The majority of participants believed that CEDs, including mixed with alcohol, were not necessarily harmful in moderation and that marketing was targeted toward older youth and young adults. Awareness of cautionary statements on CEDs was low; cautionary statements were perceived as difficult to find and read owing to the design and small font. Findings suggest a need to increase public education regarding the potential risks of CED consumption, including enhancements to the mandated cautionary statements, with greater attention to the impact of CED marketing on youth. Copyright © 2016 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

Locked and proteolysis-based transcription activator-like effector (TALE) regulation.

PubMed

Lonzarić, Jan; Lebar, Tina; Majerle, Andreja; Manček-Keber, Mateja; Jerala, Roman

2016-02-18

Development of orthogonal, designable and adjustable transcriptional regulators is an important goal of synthetic biology. Their activity has been typically modulated through stimulus-induced oligomerization or interaction between the DNA-binding and activation/repression domain. We exploited a feature of the designable Transcription activator-like effector (TALE) DNA-binding domain that it winds around the DNA which allows to topologically prevent it from binding by intramolecular cyclization. This new approach was investigated through noncovalent ligand-induced cyclization or through a covalent split intein cyclization strategy, where the topological inhibition of DNA binding by cyclization and its restoration by a proteolytic release of the topologic constraint was expected. We show that locked TALEs indeed have diminished DNA binding and regain full transcriptional activity by stimulation with the rapamycin ligand or site-specific proteolysis of the peptide linker, with much higher level of activation than rapamycin-induced heterodimerization. Additionally, we demonstrated reversibility, activation of genomic targets and implemented logic gates based on combinations of protein cyclization, proteolytic cleavage and ligand-induced dimerization, where the strongest fold induction was achieved by the proteolytic cleavage of a repression domain from a linear TALE. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Helical filaments of human Dmc1 protein on single-stranded DNA: a cautionary tale

PubMed Central

Yu, Xiong; Egelman, Edward H.

2010-01-01

Proteins in the RecA/Rad51/RadA family form nucleoprotein filaments on DNA that catalyze a strand exchange reaction as part of homologous genetic recombination. Because of the centrality of this system to many aspects of DNA repair, the generation of genetic diversity, and cancer when this system fails or is not properly regulated, these filaments have been the object of many biochemical and biophysical studies. A recent paper has argued that the human Dmc1 protein, a meiotic homolog of bacterial RecA and human Rad51, forms filaments on single stranded DNA with ∼ 9 subunits per turn in contrast to the filaments formed on double stranded DNA with ∼ 6.4 subunits per turn, and that the stoichiometry of DNA binding is different between these two filaments. We show using scanning transmission electron microscopy (STEM) that the Dmc1 filament formed on single stranded DNA has a mass per unit length expected from ∼ 6.5 subunits per turn. More generally, we show how ambiguities in helical symmetry determination can generate incorrect solutions, and why one sometimes must use other techniques, such as biochemistry, metal shadowing, or STEM to resolve these ambiguities. While three-dimensional reconstruction of helical filaments from EM images is a powerful tool, the intrinsic ambiguities that may be present with limited resolution are not sufficiently appreciated. PMID:20600108

Tris-borate is a poor counterion for RNA: a cautionary tale for RNA folding studies

PubMed Central

Buchmueller, Karen L.; Weeks, Kevin M.

2004-01-01

Native polyacrylamide gel electrophoresis is a powerful approach for visualizing RNA folding states and folding intermediates. Tris-borate has a high-buffering capacity and is therefore widely used in electrophoresis-based investigations of RNA structure and folding. However, the effectiveness of Tris-borate as a counterion for RNA has not been systematically investigated. In a recirculated Hepes/KCl buffer, the catalytic core of the bI5 group I intron RNA undergoes a conformational collapse characterized by a bulk transition midpoint, or Mg1/2, of ∼3 mM, consistent with extensive independent biochemical experiments. In contrast, in Tris-borate, RNA collapse has a much smaller apparent Mg1/2, equal to 0.1 mM, because in this buffer the RNA undergoes a different, large amplitude, folding transition at low Mg2+ concentrations. Analysis of structural neighbors using a short-lived, RNA-tethered, photocrosslinker indicates that the global RNA structure eventually converges in the two buffer systems, as the divalent ion concentration approaches ∼1 mM Mg2+. The weak capacity of Tris-borate to stabilize RNA folding may reflect relatively unfavorable interactions between the bulky Tris-borate ion and RNA or partial coordination of RNA functional groups by borate. Under some conditions, Tris-borate is a poor counterion for RNA and its use merits careful evaluation in RNA folding studies. PMID:15601995

Integrity of N- and C-termini is important for E. coli Hsp31 chaperone activity

PubMed Central

Sastry, M S R; Zhou, Weibin; Baneyx, François

2009-01-01

Hsp31 is a stress-inducible molecular chaperone involved in the management of protein misfolding at high temperatures and in the development of acid resistance in starved E. coli. Each subunit of the Hsp31 homodimer consists of two structural domains connected by a flexible linker that sits atop a continuous tract of nonpolar residues adjacent to a hydrophobic bowl defined by the dimerization interface. Previously, we proposed that while the bowl serves as a binding site for partially folded species at physiological temperatures, chaperone function under heat shock conditions requires that folding intermediates further anneal to high-affinity binding sites that become uncovered upon thermally induced motion of the linker. In support of a mechanism requiring that client proteins first bind to the bowl, we show here that fusion of a 20-residue-long hexahistidine tag to the N-termini of Hsp31 abolishes chaperone activity at all temperatures by inducing reversible structural changes that interfere with substrate binding. We further demonstrate that extending the C-termini of Hsp31 with short His tags selectively suppresses chaperone function at high temperatures by interfering with linker movement. The structural and functional sensitivity of Hsp31 to lengthening is consistent with the high degree of conservation of class I Hsp31 orthologs and will serve as a cautionary tale on the implications of affinity tagging. PMID:19517531

The science of fatty acids and inflammation.

PubMed

Fritsche, Kevin L

2015-05-01

Inflammation is believed to play a central role in many of the chronic diseases that characterize modern society. In the past decade, our understanding of how dietary fats affect our immune system and subsequently our inflammatory status has grown considerably. There are compelling data showing that high-fat meals promote endotoxin [e.g., lipopolysaccharide (LPS)] translocation into the bloodstream, stimulating innate immune cells and leading to a transient postprandial inflammatory response. The nature of this effect is influenced by the amount and type of fat consumed. The role of various dietary constituents, including fats, on gut microflora and subsequent health outcomes in the host is another exciting and novel area of inquiry. The impact of specific fatty acids on inflammation may be central to how dietary fats affect health. Three key fatty acid-inflammation interactions are briefly described. First, the evidence suggests that saturated fatty acids induce inflammation in part by mimicking the actions of LPS. Second, the often-repeated claim that dietary linoleic acid promotes inflammation was not supported in a recent systematic review of the evidence. Third, an explanation is offered for why omega-3 (n-3) polyunsaturated fatty acids are so much less anti-inflammatory in humans than in mice. The article closes with a cautionary tale from the genomic literature that illustrates why extrapolating the results from inflammation studies in mice to humans is problematic. © 2015 American Society for Nutrition.

Radiocarbon dating of planktonic foraminifer shells: A cautionary tale

NASA Astrophysics Data System (ADS)

Mekik, Figen

2014-01-01

rate, bioturbation, winnowing, and calcite dissolution produce significant radiocarbon age offsets among multiple species of coexisting planktonic foraminifers and pteropod fragments. We compare the radiocarbon age of foraminifer species and pteropod fragments with estimates of percent calcite dissolved made with a sedimentary proxy (Globorotalia menardii fragmentation index—MFI) to delineate the effect of dissolution on radiocarbon age of foraminifers. Data from two core top transects on the Rio Grande Rise (RIO) and Ontong Java Plateau (OJP) and from down core sediments of varying sedimentation rates in the tropical Pacific (ME-27, MD98 2177, and MW91-9 56GGC) reveal that sediments with the greatest accumulation rates produce the least age offsets among coexisting species. Age offsets among coexisting foraminifers are about 3500 years on RIO, and 1000 years on OJP. Two core tops from RIO yield an age of the Last Glacial Maximum possibly due to mass displacement of younger sediments downslope. Foraminifer age increases with increasing dissolution and there is a consistent pattern of older foraminifer fragments coexisting with younger whole shells of the same species. The only exception is sediments which have experienced high dissolution where fragments are younger than whole shells. The age offset between fragments of G. menardii and its coexisting whole shells does not exceed the age offset among other coexisting foraminifer species in the same core tops.

A Statistician's View of Upcoming Grand Challenges

NASA Astrophysics Data System (ADS)

Meng, Xiao Li

2010-01-01

In this session we have seen some snapshots of the broad spectrum of challenges, in this age of huge, complex, computer-intensive models, data, instruments,and questions. These challenges bridge astronomy at many wavelengths; basic physics; machine learning; -- and statistics. At one end of our spectrum, we think of 'compressing' the data with non-parametric methods. This raises the question of creating 'pseudo-replicas' of the data for uncertainty estimates. What would be involved in, e.g. boot-strap and related methods? Somewhere in the middle are these non-parametric methods for encapsulating the uncertainty information. At the far end, we find more model-based approaches, with the physics model embedded in the likelihood and analysis. The other distinctive problem is really the 'black-box' problem, where one has a complicated e.g. fundamental physics-based computer code, or 'black box', and one needs to know how changing the parameters at input -- due to uncertainties of any kind -- will map to changing the output. All of these connect to challenges in complexity of data and computation speed. Dr. Meng will highlight ways to 'cut corners' with advanced computational techniques, such as Parallel Tempering and Equal Energy methods. As well, there are cautionary tales of running automated analysis with real data -- where "30 sigma" outliers due to data artifacts can be more common than the astrophysical event of interest.

The vulnerability of being ill informed: the Trans-Pacific Partnership Agreement and Global Public Health.

PubMed

Greenberg, Henry; Shiau, Stephanie

2014-09-01

The Trans Pacific Partnership Agreement (TPPA) is a regional trade agreement currently being negotiated by 11 Pacific Rim countries, excluding China. While the negotiations are being conducted under a veil of secrecy, substantive leaks over the past 4 years have revealed a broad view of the proposed contents. As it stands the TPPA poses serious risks to global public health, particularly chronic, non-communicable diseases. At greatest risk are national tobacco regulations, regulations governing the emergence of generic drugs and controls over food imports by transnational corporations. Aside from a small group of public health professionals from Australia, the academic public health community has missed these threats to the global community, although many other health-related entities, international lawyers and health-conscious politicians have voiced serious concerns. As of mid-2014 there has been no comment in the leading public health journals. This large lacuna in interest or recognition reflects the larger problem that the public health education community has all but ignored global non-communicable diseases. Without such a focus, the risks are unseen and the threats not perceived. This cautionary tale of the TPPA reflects the vulnerability of being ill informed of contemporary realities. © The Author 2014. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Postoperative rhabdomyolysis following robotic renal and adrenal surgery: a cautionary tale of compounding risk factors.

PubMed

Terry, Russell S; Gerke, Travis; Mason, James B; Sorensen, Matthew D; Joseph, Jason P; Dahm, Philipp; Su, Li-Ming

2015-09-01

This study aimed at reviewing a contemporary series of patients who underwent robotic renal and adrenal surgery by a single surgeon at a tertiary referral academic medical center over a 6-year period, specifically focusing on the unique and serious complication of post-operative rhabdomyolysis of the dependent lower extremity. The cases of 315 consecutive patients who underwent robotic upper tract surgery over a 6-year period from August 2008 to June 2014 using a standardized patient positioning were reviewed and analyzed for patient characteristics and surgical variables that may be associated with the development of post-operative rhabdomyolysis. The incidence of post-operative rhabdomyolysis in our series was 3/315 (0.95%). All three affected patients had undergone robotic nephroureterectomy. Those patients who developed rhabdomyolysis had significantly higher mean Body Mass Index, Charlson Comorbidity Index, and median length of stay than those who did not. The mean OR time in the rhabdomyolysis group was noted to be 52 min longer than the non-rhabdomyolysis group, though this value did not reach statistical significance. Given the trends of increasing obesity in the United States and abroad as well as the continued rise in robotic upper tract urologic surgeries, urologists need to be increasingly vigilant for recognizing the risk factors and early treatment of the unique complication of post-operative rhabdomyolysis.

Content Volatility of Scientific Topics in Wikipedia: A Cautionary Tale.

PubMed

Wilson, Adam M; Likens, Gene E

2015-01-01

Wikipedia has quickly become one of the most frequently accessed encyclopedic references, despite the ease with which content can be changed and the potential for 'edit wars' surrounding controversial topics. Little is known about how this potential for controversy affects the accuracy and stability of information on scientific topics, especially those with associated political controversy. Here we present an analysis of the Wikipedia edit histories for seven scientific articles and show that topics we consider politically but not scientifically "controversial" (such as evolution and global warming) experience more frequent edits with more words changed per day than pages we consider "noncontroversial" (such as the standard model in physics or heliocentrism). For example, over the period we analyzed, the global warming page was edited on average (geometric mean ±SD) 1.9±2.7 times resulting in 110.9±10.3 words changed per day, while the standard model in physics was only edited 0.2±1.4 times resulting in 9.4±5.0 words changed per day. The high rate of change observed in these pages makes it difficult for experts to monitor accuracy and contribute time-consuming corrections, to the possible detriment of scientific accuracy. As our society turns to Wikipedia as a primary source of scientific information, it is vital we read it critically and with the understanding that the content is dynamic and vulnerable to vandalism and other shenanigans.

The Hippocratic need for adequate supports while merging programs: at first do no harm

NASA Astrophysics Data System (ADS)

Sipple, John W.

2017-03-01

In response to a paper calling for the re-engagement of agricultural education with the sciences and science education, this essay is supportive but argues to proceed with caution: one that at first does no harm. I offer a supplementary lens and story of change at Cornell University as a cautionary and motivational tale. I concur with the authors who want to redirect faculty, departments, and societies of agricultural educators to become more tightly aligned with the sciences. The need for and ability to better contribute to the critical discussions on contemporary agriculture issues (e.g., urban farming, GMOs, sustainability, local economies) is timely and important. The trick, however, is to do this without weakening the agricultural education community to the point of extinction. Drawing on Institutional Theory, I offer an enhanced perspective highlighting the importance of resource, conformity, and legitimacy. I explore the nature of competing pressures: the strong and restrictive ties to isolated communities and the pressure to reengage a community with a more socially and intellectually central world. I want to emphasize how these strong ties are typically beneficial to the organizations of interest, despite what it may look like to others outside that sector. It is argued that agricultural education will become increasingly "vulnerable and isolated" should it not cross the street and at least partially connect with contemporary science, social science, and new policy and ethical concerns.

Unexpected Cartilage Phenotype in CD4-Cre-Conditional SOS-Deficient Mice.

PubMed

Guittard, Geoffrey; Gallardo, Devorah L; Li, Wenmei; Melis, Nicolas; Lui, Julian C; Kortum, Robert L; Shakarishvili, Nicholas G; Huh, Sunmee; Baron, Jeffrey; Weigert, Roberto; Kramer, Joshua A; Samelson, Lawrence E; Sommers, Connie L

2017-01-01

RAS signaling is central to many cellular processes and SOS proteins promote RAS activation. To investigate the role of SOS proteins in T cell biology, we crossed Sos1 f/f Sos2 -/- mice to CD4-Cre transgenic mice. We previously reported an effect of these mutations on T cell signaling and T cell migration. Unexpectedly, we observed nodules on the joints of greater than 90% of these mutant mice at 5 months of age, especially on the carpal joints. As the mice aged further, some also displayed joint stiffness, hind limb paralysis, and lameness. Histological analysis indicated that the abnormal growth in joints originated from dysplastic chondrocytes. Second harmonic generation imaging of the carpal nodules revealed that nodules were encased by rich collagen fibrous networks. Nodules formed in mice also deficient in RAG2, indicating that conventional T cells, which undergo rearrangement of the T cell antigen receptor, are not required for this phenotype. CD4-Cre expression in a subset of cells, either immune lineage cells (e.g., non-conventional T cells) or non-immune lineage cells (e.g., chondrocytes) likely mediates the dramatic phenotype observed in this study. Disruptions of genes in the RAS signaling pathway are especially likely to cause this phenotype. These results also serve as a cautionary tale to those intending to use CD4-Cre transgenic mice to specifically delete genes in conventional T cells.

XA23 is an executor R protein and confers broad-spectrum disease resistance in rice.

PubMed

Wang, Chunlian; Zhang, Xiaoping; Fan, Yinglun; Gao, Ying; Zhu, Qinlong; Zheng, Chongke; Qin, Tengfei; Li, Yanqiang; Che, Jinying; Zhang, Mingwei; Yang, Bing; Liu, Yaoguang; Zhao, Kaijun

2014-11-09

The majority of plant disease resistance (R) genes encode proteins that share common structural features. However, the transcription activator-like effector (TALE) associated executor type R genes show no considerable sequence homology to any known R genes. We adopted a map-based cloning approach and TALE-based technology to isolate and characterize Xa23, a new executor R gene derived from the wild rice (Oryza rufipogon) that confers an extremely broad spectrum of resistance to bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo). Xa23 encodes a 113-amino acid protein that shares 50% identity to the known executor R protein XA10. The predicted transmembrane helices in XA23 also overlap with those of XA10. Unlike Xa10, however, Xa23 transcription is specifically activated by AvrXa23, a TALE present in all examined Xoo field isolates. Moreover, the susceptible xa23 allele has an identical open reading frame of Xa23, but differs in promoter region by lacking the TALE binding-element (EBE) for AvrXa23. XA23 can trigger strong hypersensitive response in rice, tobacco and tomato. Our results provide the first evidence that plant genomes have an executor R gene family in which members execute their function and spectrum of disease resistance by recognizing the cognate TALEs in pathogen. © The Author 2014. Published by the Molecular Plant Shanghai Editorial Office in association with Oxford University Press on behalf of CSPB and IPPE, SIBS, CAS.

Spectrum measurement with the Telescope Array Low Energy Extension (TALE) fluorescence detector

NASA Astrophysics Data System (ADS)

Zundel, Zachary James

The Telescope Array (TA) experiment is the largest Ultra High Energy cosmic ray observatory in the northern hemisphere and is designed to be sensitive to cosmic ray air showers above 1018eV. Despite the substantial measurements made by TA and AUGER (the largest cosmic ray observatory in the southern hemisphere), there remains uncertainty about whether the highest energy cosmic rays are galactic or extragalactic in origin. Locating features in the cosmic ray energy spectrum below 1018eV that indicate a transition from galactic to extragalactic sources would clarify the interpretation of measurements made at the highest energies. The Telescope Array Low Energy Extension (TALE) is designed to extend the energy threshold of the TA observatory down to 1016.5eV in order to make such measurements. This dissertation details the construction, calibration, and operation of the TALE flu- orescence detector. A measurement of the flux of cosmic rays in the energy range of 1016.5 -- 1018.5eV is made using the monocular data set taken between September 2013 and January 2014. The TALE fluorescence detector observes evidence for a softening of the cosmic spectrum at 1017.25+/-0.5eV. The evidence of a change in the spectrum motivates continued study of 1016.5 -- 1018.5eV cosmic rays.

Directed evolution of the TALE N-terminal domain for recognition of all 5' bases.

PubMed

Lamb, Brian M; Mercer, Andrew C; Barbas, Carlos F

2013-11-01

Transcription activator-like effector (TALE) proteins can be designed to bind virtually any DNA sequence. General guidelines for design of TALE DNA-binding domains suggest that the 5'-most base of the DNA sequence bound by the TALE (the N0 base) should be a thymine. We quantified the N0 requirement by analysis of the activities of TALE transcription factors (TALE-TF), TALE recombinases (TALE-R) and TALE nucleases (TALENs) with each DNA base at this position. In the absence of a 5' T, we observed decreases in TALE activity up to >1000-fold in TALE-TF activity, up to 100-fold in TALE-R activity and up to 10-fold reduction in TALEN activity compared with target sequences containing a 5' T. To develop TALE architectures that recognize all possible N0 bases, we used structure-guided library design coupled with TALE-R activity selections to evolve novel TALE N-terminal domains to accommodate any N0 base. A G-selective domain and broadly reactive domains were isolated and characterized. The engineered TALE domains selected in the TALE-R format demonstrated modularity and were active in TALE-TF and TALEN architectures. Evolved N-terminal domains provide effective and unconstrained TALE-based targeting of any DNA sequence as TALE binding proteins and designer enzymes.

Directed evolution of the TALE N-terminal domain for recognition of all 5′ bases

PubMed Central

Lamb, Brian M.; Mercer, Andrew C.; Barbas, Carlos F.

2013-01-01

Transcription activator-like effector (TALE) proteins can be designed to bind virtually any DNA sequence. General guidelines for design of TALE DNA-binding domains suggest that the 5′-most base of the DNA sequence bound by the TALE (the N0 base) should be a thymine. We quantified the N0 requirement by analysis of the activities of TALE transcription factors (TALE-TF), TALE recombinases (TALE-R) and TALE nucleases (TALENs) with each DNA base at this position. In the absence of a 5′ T, we observed decreases in TALE activity up to >1000-fold in TALE-TF activity, up to 100-fold in TALE-R activity and up to 10-fold reduction in TALEN activity compared with target sequences containing a 5′ T. To develop TALE architectures that recognize all possible N0 bases, we used structure-guided library design coupled with TALE-R activity selections to evolve novel TALE N-terminal domains to accommodate any N0 base. A G-selective domain and broadly reactive domains were isolated and characterized. The engineered TALE domains selected in the TALE-R format demonstrated modularity and were active in TALE-TF and TALEN architectures. Evolved N-terminal domains provide effective and unconstrained TALE-based targeting of any DNA sequence as TALE binding proteins and designer enzymes. PMID:23980031

AnnoTALE: bioinformatics tools for identification, annotation, and nomenclature of TALEs from Xanthomonas genomic sequences

PubMed Central

Grau, Jan; Reschke, Maik; Erkes, Annett; Streubel, Jana; Morgan, Richard D.; Wilson, Geoffrey G.; Koebnik, Ralf; Boch, Jens

2016-01-01

Transcription activator-like effectors (TALEs) are virulence factors, produced by the bacterial plant-pathogen Xanthomonas, that function as gene activators inside plant cells. Although the contribution of individual TALEs to infectivity has been shown, the specific roles of most TALEs, and the overall TALE diversity in Xanthomonas spp. is not known. TALEs possess a highly repetitive DNA-binding domain, which is notoriously difficult to sequence. Here, we describe an improved method for characterizing TALE genes by the use of PacBio sequencing. We present ‘AnnoTALE’, a suite of applications for the analysis and annotation of TALE genes from Xanthomonas genomes, and for grouping similar TALEs into classes. Based on these classes, we propose a unified nomenclature for Xanthomonas TALEs that reveals similarities pointing to related functionalities. This new classification enables us to compare related TALEs and to identify base substitutions responsible for the evolution of TALE specificities. PMID:26876161

Kepler Transit Depths Contaminated By a Phantom Star

NASA Astrophysics Data System (ADS)

Dalba, Paul A.; Muirhead, Philip S.; Croll, Bryce; Kempton, Eliza M.-R.

2017-02-01

We present ground-based observations from the Discovery Channel Telescope (DCT) of three transits of Kepler-445c—a supposed super-Earth exoplanet with properties resembling GJ 1214b—and demonstrate that the transit depth is ˜50% shallower than the depth previously inferred from Kepler spacecraft data. The resulting decrease in planetary radius significantly alters the interpretation of the exoplanet’s bulk composition. Despite the faintness of the M4 dwarf host star, our ground-based photometry clearly recovers each transit and achieves repeatable 1σ precision of ˜0.2% (2 millimags). The transit parameters estimated from the DCT data are discrepant with those inferred from the Kepler data to at least 17σ confidence. This inconsistency is due to a subtle miscalculation of the stellar crowding metric during the Kepler pre-search data conditioning (PDC). The crowding metric, or CROWDSAP, is contaminated by a non-existent phantom star originating in the USNO-B1 catalog and inherited by the Kepler Input Catalog (KIC). Phantom stars in the KIC are likely rare, but they have the potential to affect statistical studies of Kepler targets that use the PDC transit depths for a large number of exoplanets where an individual follow-up observation of each is not possible. The miscalculation of Kepler-445c’s transit depth emphasizes the importance of stellar crowding in the Kepler data, and provides a cautionary tale for the analysis of data from the Transiting Exoplanet Survey Satellite, which will have even larger pixels than Kepler.

Penetrating head injury from angle grinder: A cautionary tale.

PubMed

Senthilkumaran, S; Balamurgan, N; Arthanari, K; Thirumalaikolundusubramanian, P

2010-01-01

Penetrating cranial injury is a potentially life-threatening condition. Injuries resulting from the use of angle grinders are numerous and cause high-velocity penetrating cranial injuries. We present a series of two penetrating head injuries associated with improper use of angle grinder, which resulted in shattering of disc into high velocity missiles with reference to management and prevention. One of those hit on the forehead of the operator and the other on the occipital region of the co-worker at a distance of five meters. The pathophysiological consequence of penetrating head injuries depends on the kinetic energy and trajectory of the object. In the nearby healthcare center the impacted broken disc was removed without realising the consequences and the wound was packed. As the conscious level declined in both, they were referred. CT brain revealed fracture in skull and changes in the brain in both. Expeditious removal of the penetrating foreign body and focal debridement of the scalp, skull, dura, and involved parenchyma and Watertight dural closure were carried out. The most important thing is not to remove the impacted foreign body at the site of accident. Craniectomy around the foreign body, debridement and removal of foreign body without zigzag motion are needed. Removal should be done following original direction of projectile injury. The neurological sequelae following the non missile penetrating head injuries are determined by the severity and location of initial injury as well as the rapidity of the exploration and fastidious debridement.

Evidence for a Common Origin of Blacksmiths and Cultivators in the Ethiopian Ari within the Last 4500 Years: Lessons for Clustering-Based Inference

PubMed Central

van Dorp, Lucy; Balding, David; Myers, Simon; Pagani, Luca; Tyler-Smith, Chris; Bekele, Endashaw; Tarekegn, Ayele; Thomas, Mark G.; Bradman, Neil; Hellenthal, Garrett

2015-01-01

The Ari peoples of Ethiopia are comprised of different occupational groups that can be distinguished genetically, with Ari Cultivators and the socially marginalised Ari Blacksmiths recently shown to have a similar level of genetic differentiation between them (F ST ≈ 0.023 − 0.04) as that observed among multiple ethnic groups sampled throughout Ethiopia. Anthropologists have proposed two competing theories to explain the origins of the Ari Blacksmiths as (i) remnants of a population that inhabited Ethiopia prior to the arrival of agriculturists (e.g. Cultivators), or (ii) relatively recently related to the Cultivators but presently marginalized in the community due to their trade. Two recent studies by different groups analysed genome-wide DNA from samples of Ari Blacksmiths and Cultivators and suggested that genetic patterns between the two groups were more consistent with model (i) and subsequent assimilation of the indigenous peoples into the expanding agriculturalist community. We analysed the same samples using approaches designed to attenuate signals of genetic differentiation that are attributable to allelic drift within a population. By doing so, we provide evidence that the genetic differences between Ari Blacksmiths and Cultivators can be entirely explained by bottleneck effects consistent with hypothesis (ii). This finding serves as both a cautionary tale about interpreting results from unsupervised clustering algorithms, and suggests that social constructions are contributing directly to genetic differentiation over a relatively short time period among previously genetically similar groups. PMID:26291793

Prunus africana (Hook.f.) Kalkman: the overexploitation of a medicinal plant species and its legal context.

PubMed

Bodeker, Gerard; van 't Klooster, Charlotte; Weisbord, Emma

2014-11-01

The linkage between herbal medicines and the sustainability of medical plants from which they are manufactured is increasingly being understood and receiving attention through international accords and trade labeling systems. However, little attention is paid to the fair trade aspects of this sector, including the issue of benefit-sharing agreements with traditional societies whose knowledge and resources are being exploited for commercial herbal medicine development and production. This article examines the case of Prunus africana (Hook.f.) Kalkman, from equatorial Africa. While the conservation and cultivation dimension of the trade in P. africana has been much discussed in literature, no research appears to have focused on the traditional resource rights and related ethical dimensions of this trade in traditional medicine of Africa. Serving as a cautionary tale for the unbridled exploitation of medicinal plants, the history of P. africana extraction is considered here in the context of relevant treaties and agreements existing today. These include the Nagoya Protocol, a supplementary agreement to the Convention on Biological Diversity, the Trade-Related Aspects of Intellectual Property Rights agreement from the World Trade Organization, and two African regional frameworks: the Swakopmund Protocol and the Organisation Africaine de la Propriété Intellectuelle Initiative. In the context of strengthening medicinal plant research in Africa, a novel international capacity-building project on traditional medicines for better public health in Africa will be discussed, illustrating how access and benefit sharing principles might be incorporated in future projects on traditional medicines.

Helical filaments of human Dmc1 protein on single-stranded DNA: a cautionary tale.

PubMed

Yu, Xiong; Egelman, Edward H

2010-08-20

Proteins in the RecA/Rad51/RadA family form nucleoprotein filaments on DNA that catalyze a strand exchange reaction as part of homologous genetic recombination. Because of the centrality of this system to many aspects of DNA repair, the generation of genetic diversity, and cancer when this system fails or is not properly regulated, these filaments have been the object of many biochemical and biophysical studies. A recent paper has argued that the human Dmc1 protein, a meiotic homolog of bacterial RecA and human Rad51, forms filaments on single-stranded DNA with approximately 9 subunits per turn in contrast to the filaments formed on double-stranded DNA with approximately 6.4 subunits per turn and that the stoichiometry of DNA binding is different between these two filaments. We show using scanning transmission electron microscopy that the Dmc1 filament formed on single-stranded DNA has a mass per unit length expected from approximately 6.5 subunits per turn. More generally, we show how ambiguities in helical symmetry determination can generate incorrect solutions and why one sometimes must use other techniques, such as biochemistry, metal shadowing, or scanning transmission electron microscopy, to resolve these ambiguities. While three-dimensional reconstruction of helical filaments from EM images is a powerful tool, the intrinsic ambiguities that may be present with limited resolution are not sufficiently appreciated. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

How Has Educational Expansion Shaped Social Mobility Trends in the United States?

PubMed Central

Pfeffer, Fabian T.; Hertel, Florian R.

2015-01-01

This contribution provides a long-term assessment of intergenerational social mobility trends in the United States across the 20th and early 21st century and assesses the determinants of those trends. In particular, we study how educational expansion has contributed to the observed changes in mobility opportunities for men across cohorts. Drawing on recently developed decomposition methods, we empirically identify the contribution of each of the multiple channels through which changing rates of educational participation shape mobility trends. We find that a modest but gradual increase in social class mobility can nearly exclusively be ascribed to an interaction known as the compositional effect, according to which the direct influence of social class backgrounds on social class destinations is lower among the growing number of individuals attaining higher levels of education. This dominant role of the compositional effect is also due to the fact that, despite pronounced changes in the distribution of education, class inequality in education has remained stable while class returns to education have shown no consistent trend. Our analyses also provide a cautionary tale about mistaking increasing levels of social class mobility for a general trend towards more fluidity in the United States. The impact of parental education on son's educational and class attainment has grown or remained stable, respectively. Here, the compositional effect pertaining to the direct association between parental education and son's class attainment counteracts a long-term trend of increasing inequality in educational attainment tied to parents' education. PMID:26306053

Chasing maximal performance: a cautionary tale from the celebrated jumping frogs of Calaveras County.

PubMed

Astley, H C; Abbott, E M; Azizi, E; Marsh, R L; Roberts, T J

2013-11-01

Maximal performance is an essential metric for understanding many aspects of an organism's biology, but it can be difficult to determine because a measured maximum may reflect only a peak level of effort, not a physiological limit. We used a unique opportunity provided by a frog jumping contest to evaluate the validity of existing laboratory estimates of maximum jumping performance in bullfrogs (Rana catesbeiana). We recorded video of 3124 bullfrog jumps over the course of the 4-day contest at the Calaveras County Jumping Frog Jubilee, and determined jump distance from these images and a calibration of the jump arena. Frogs were divided into two groups: 'rental' frogs collected by fair organizers and jumped by the general public, and frogs collected and jumped by experienced, 'professional' teams. A total of 58% of recorded jumps surpassed the maximum jump distance in the literature (1.295 m), and the longest jump was 2.2 m. Compared with rental frogs, professionally jumped frogs jumped farther, and the distribution of jump distances for this group was skewed towards long jumps. Calculated muscular work, historical records and the skewed distribution of jump distances all suggest that the longest jumps represent the true performance limit for this species. Using resampling, we estimated the probability of observing a given jump distance for various sample sizes, showing that large sample sizes are required to detect rare maximal jumps. These results show the importance of sample size, animal motivation and physiological conditions for accurate maximal performance estimates.

The Strengthening Effect of Ice on Two Extraterrestrial Analogs: A Cautionary Tale

NASA Astrophysics Data System (ADS)

Atkinson, J.; Durham, W. B.; Seager, S.

2016-12-01

Sample retrieval from extraterrestrial bodies and in situ resource utilization (ISRU) activities have been identified as some of the most important scientific endeavors of the coming decade. With the failure of Rosetta's Philae lander to penetrate the surface of comet 67P and obtain a sample due to the high compressive strength of the surface, it is becoming obvious that knowledge of the mechanical properties of materials that might be encountered in such environments and under such conditions is critical to future mission success. Two comet/asteroid analogs (Indiana limestone and Bishop tuff), selected based on their contrasting mechanical properties and porosities, were tested under constant displacement to failure (in most cases) at low temperatures (295 K to 77 K) and low confining pressures (1 to 5 MPa). The compressive strength of both materials was determined under varied conditions of saturation, from oven-dried ( 0% water content) to fully saturated, and both brittle and ductile behavior was observed. The saturated limestone increased in strength from 30 MPa (at 295 K) to >200 MPa (at 77 K), while the Bishop tuff increased in strength from 13 MPa at 295 K to 165 MPa at 150 K. The results of this study will be useful to future sample retrieval missions or ISRU maneuvers. The large increase in compressive strength of these saturated materials at cryogenic temperatures means that future missions will need to prepare technology that has the energetic and mechanical capability to penetrate very hard substrates as they are likely to encounter.

What's in a name? Tensions between formal and informal communities of practice among regional subspecialty cancer surgeons.

PubMed

Kitto, Simon C; Grant, Rachel E; Peller, Jennifer; Moulton, Carol-Anne; Gallinger, Steven

2018-03-01

In 2007 the Cancer Care Ontario Hepatobiliary-Pancreatic (HPB) Community of Practice was formed during the wake of provincial regionalization of HPB services in Ontario, Canada. Despite being conceptualized within the literature as an educational intervention, communities of practice (CoP) are increasingly being adopted in healthcare as quality improvement initiatives. A qualitative case study approach using in-depth interviews and document analysis was employed to gain insight into the perceptions and attitudes of the HPB surgeons in the CoP. This study demonstrates how an engineered formal or idealized structure of a CoP was created in tension with the natural CoPs that HPB surgeons identified with during and after their training. This tension contributed to the inactive and/or marginal participation by some of the surgeons in the CoP. The findings of this study represent a cautionary tale for such future engineering attempts in two distinct ways: (1) a CoP in surgery cannot simply be created by regulatory agencies, rather they need to be supported in a way to evolve naturally, and (2) when the concept of CoPs is co-opted by governing bodies, it does not necessarily capture the power and potential of situated learning. To ensure CoP sustainability and effectiveness, we suggest that both core and peripheral members need to be more directly involved at the inception of the COP in terms of design, organization, implementation and ongoing management.

Cullen, a cautionary tale.

PubMed

Dyde, Sean

2015-04-01

Some ideas return after the briefest of exiles: reductionism is back in vogue. Existential questions - about who we are, about our origins and future, about what is valuable - no longer require difficult soul searching, especially when straightforward answers are expected from the neurosciences. History is being rewritten with the brain as its centrepiece; the search for great men and big ideas of the past begins again. William Cullen (1710-90), whose work on neurosis was once part of the history of psychoanalysis, is now well placed to become part of such a neuro-history. This article attempts to subvert this process, by rebuilding the original meaning of neurosis through Cullen's physiological and medical works, in comparison with his predecessor, Robert Whytt (1714-66), and illustrating this meaning using one particular neurosis: hypochondriasis. The result is a more complicated version of neurosis which, importantly, carries significant insights into the nature and practice of medicine. Moreover, this article examines how Cullen's standing fell in the 1820s as British physicians and surgeons turned to an idea which promised to reform medicine: pathological anatomy. When these hopes faded, Cullen became a figure obsessed with the nerves. This image has survived to the present, a blank canvas onto which any theory can be projected. It also values precisely what Cullen warned against: simplistic explanations of the body and disease, and unthinking confidence in the next big idea or silver bullet. Neurosis was not simply a nervous ailment, but it is a warning against reductionism in history making.

The Ethical Implications of Cultural Intervention by Space-faring Civilizations -- What Science Fiction Has to Say

NASA Astrophysics Data System (ADS)

Ciupa, M.

Science fiction (Scifi) plays out the concerns of our possible scientistic futures; it is a source for exploring the deep rooted psychological concerns of mankind with science and the humanities. In this paper it is proposed Scifi is a valid source of hypotheses to examine, not as "evidence", but as candidate ­ often cautionary ­ notions, i.e., scenarios to be studied. Scifi represents a kind of Jungian mythological based story-telling, putting forward tales that express our conscious/unconscious concerns. Thus, when looking into ethical questions like, "where will techno-progressive futures take us?", we import into them these archetypes, hopes and fears, as a result they frequently reappear as familiar tropes. In this respect it is appropriate not to ignore them, but to openly challenge/appreciate them: to see what scenarios are indeed likely and how they may impact us reciprocally. This paper examines some of these aspects, and provides examples of how they are represented in the Scifi genre, in particular with consideration of the ethical implications of cultural intervention by space-faring civilizations. Given the specific analysis/examples provided, it concludes with an ethical scenario analysis (a dialectic argument), within the limiting conditions of the Drake Equation, Fermi Paradox and Cultural History. It comments on the potential existential risk of the Active SETI programmes recently initiated, indeed the need for an ethical exosociological review of all proposed Interstellar projects that express an "Intervention-Propensity".

Cyprus as a degraded landscape or resilient environment in the wake of colonial intrusion

PubMed Central

Harris, Sarah E.

2012-01-01

Concerns about global warming, degradation of fragile ecosystems, and environmental and societal collapse have increased interest for lessons and/or solutions for today's environmental issues. Popular writers have turned to a classic degradation thesis of deforestation and presumed desertification within the Eastern Mediterranean as a cautionary tale of how past societies have committed ecological suicide. However, degradation and/or collapse is far more complex than the thesis permits, and uncritical adoption of such simplified stories encourages continued use of inaccurate assumptions about human–environment interaction. In Cyprus, such a degradation story materialized 150 y ago, and its promoters aimed to impress on readers their responsibility to reverse past environmental mistakes. Both the British Colonial authorities (1878–1960) and the post-Independence Cypriot government used it to justify their environmental policies. Unfortunately, this thesis was formed around several misunderstandings about Cypriot environments and society: (i) judgment of degradation without appropriate consideration of the difference between degradation and change; (ii) oversimplified representation of ruling powers and those people ruled; and (iii) denigration of the shepherd lifestyle and its presumed environmental impact. A multimethod approach using archival and field research offers a more nuanced understanding of the complexity of human–environment interaction, the underappreciated environmental and societal resilience of areas classified as degraded, and the importance of placing events within changing socioeconomic and political contexts. This study of natural resource management and environmental resilience illustrates that the practices that the colonial government viewed as unsustainable likely were sustainable. PMID:22371577

Cyprus as a degraded landscape or resilient environment in the wake of colonial intrusion.

PubMed

Harris, Sarah E

2012-03-06

Concerns about global warming, degradation of fragile ecosystems, and environmental and societal collapse have increased interest for lessons and/or solutions for today's environmental issues. Popular writers have turned to a classic degradation thesis of deforestation and presumed desertification within the Eastern Mediterranean as a cautionary tale of how past societies have committed ecological suicide. However, degradation and/or collapse is far more complex than the thesis permits, and uncritical adoption of such simplified stories encourages continued use of inaccurate assumptions about human-environment interaction. In Cyprus, such a degradation story materialized 150 y ago, and its promoters aimed to impress on readers their responsibility to reverse past environmental mistakes. Both the British Colonial authorities (1878-1960) and the post-Independence Cypriot government used it to justify their environmental policies. Unfortunately, this thesis was formed around several misunderstandings about Cypriot environments and society: (i) judgment of degradation without appropriate consideration of the difference between degradation and change; (ii) oversimplified representation of ruling powers and those people ruled; and (iii) denigration of the shepherd lifestyle and its presumed environmental impact. A multimethod approach using archival and field research offers a more nuanced understanding of the complexity of human-environment interaction, the underappreciated environmental and societal resilience of areas classified as degraded, and the importance of placing events within changing socioeconomic and political contexts. This study of natural resource management and environmental resilience illustrates that the practices that the colonial government viewed as unsustainable likely were sustainable.

The last half-repeat of transcription activator-like effector (TALE) is dispensable and thereby TALE-based technology can be simplified.

PubMed

Zheng, Chong-Ke; Wang, Chun-Lian; Zhang, Xiao-Ping; Wang, Fu-Jun; Qin, Teng-Fei; Zhao, Kai-Jun

2014-09-01

To activate the expression of host genes that contribute to pathogen growth, pathogenic Xanthomonas bacteria inject their transcription activator-like effectors (TALEs) into plant cells and the TALEs bind to target gene promoters by the central repeat region consisting of near-perfect 34-amino-acid repeats (34-aa repeats). Based on the recognition codes between the 34-aa repeats and the targeted nucleotides, TALE-based technologies, such as designer TALEs (dTALEs) and TALE nucleases (TALENs), have been developed. Amazingly, every natural TALE invariantly has a truncated last half-repeat (LHR) at the end of the 34-aa repeats. Consequently, all the reported dTALEs and TALENs also harbour their LHRs. Here, we show that the LHRs in dTALEs are dispensable for the function of gene activation by both transient expression assays in Nicotiana benthamiana and gene-specific targeting in the rice genome, indicating that TALEs might originate from a single progenitor. In the light of this finding, we demonstrate that dTALEs can be constructed through two simple steps. Moreover, the activation strengths of dTALEs lacking the LHR are comparable with those of dTALEs harbouring the LHR. Our results provide new insights into the origin of natural TALEs, and will facilitate the simplification of the design and assembly of TALE-based tools, such as dTALEs and TALENs, in the near future. © 2014 BSPP AND JOHN WILEY & SONS LTD.

Peace--Iowa's Link.

ERIC Educational Resources Information Center

Gore, Deborah, Ed.

1991-01-01

This theme journal issue is devoted to an exploration of peace and its history in Iowa. The features and activities include: Iowa's Peace Tradition; A Global View; World Map; A Mesquakie Tale; Swords into Plowshares; Make a Peace Crane; Student Protest; Goldfinch Patriotism Debate; Peace Meal; A Short Story; and Work It Out. (DB)

"Soperezhivanie": Dramatic Events in Fairy Tales and Play

ERIC Educational Resources Information Center

March, Sue; Fleer, Marilyn

2016-01-01

The concept of "perezhivanie" has gained theoretical attention and is beginning to feature in empirical studies of young children, where the role of emotion is foregrounded (e.g., Ferholt, 2010). However, the idea of a "collective perezhivanie" of adults and children in early childhood settings has not yet been researched. In…

Effects of cautionary messages and vulnerability factors on viewers' perceptions of alcohol advertisements.

PubMed

Proctor, Dwayne C; Babor, Thomas F; Xuan, Ziming

2005-09-01

This study examined how individual difference vulnerability factors affect college students' perceptions of beer commercial actors' age, attractiveness and drinking. We were also interested in whether viewers' exposure to a cautionary message would affect their perceptions of the actors' drinking behavior. Three groups of college students were exposed to the same set of two alcohol advertisements. After watching the ads, each group received a different cautionary message prior to answering questions about the ad's content: (1) a neutral message (viewed by 42% [n = 119] of the sample), (2) a U.S. federal warning (viewed by 31% [n = 89]) and (3) an industry message (viewed by 27% [n = 76]). We also examined three putative vulnerability factors: age (underage 21 or not), gender and family history of alcohol problems (yes or no) as well as the effects of quantity-frequency of alcohol consumption, episodic heavy drinking, severity of alcohol dependence, disinhibition sensation seeking and the eight factors of the Alcohol Expectancy Scale. The cautionary messages had no effect on viewers' perceptions of characters' age, attractiveness and drinking behavior. Although neither of the commercials depicted the physical act of drinking, the student raters nevertheless perceived the characters to be heavy episodic drinkers. Those reporting more alcohol dependence symptoms perceived increased drinking for the male characters, as did females and viewers with expectancies for social and physical pleasure. Perceptions of the drinking in beer commercials are based in part on the character depicted in the ad and in part on the demographic and personal vulnerability factors of the viewer.

Three Cheers for the Red, White, and Blue!

ERIC Educational Resources Information Center

Instructor, 1983

1983-01-01

This package of patriotic learning activities refers to historic tales about colonial days, Black history, and the contributions of the states to America's wealth and history. Poems, skits, riddles about states and presidents, and a play featuring mock presidential interviews are included. A Save-the-Statue-of-Liberty project is noted. (PP)

Reviews of 12 Books, Magazines, and Other Materials for American Indian Students and Their Teachers .

ERIC Educational Resources Information Center

Independent American Indian Review, 1995

1995-01-01

Recommends seven books about American Indian culture, history, folk tales, leaders, and philosophy; a calendar featuring Navajo professional women; three magazines focusing on Arizona Indian nations, contemporary Native arts and music, and multicultural education; and CD or cassette of contemporary Native instrumental music. Includes bibliographic…

Fables and Trickster Tales around the World. [Lesson Plan].

ERIC Educational Resources Information Center

2002

Fables and trickster stories are short narratives that use animal characters with human features to convey folk wisdom and to help people understand human nature and human behavior. These stories were originally passed down through oral tradition and were eventually written down. These lesson plans are intended for students in grades 3-5 and…

A Tale of the Field: Reading Power and Gender in the Learning Organization

ERIC Educational Resources Information Center

Alexiou, Anna

2005-01-01

In this article, I will argue that learning organizations that claim certain emancipatory promises in principle continue to ignore issues of gender, which, in practice are a distinctive and defining feature of our workplace contexts. Applying a feminist?Foucauldian interpretive framework, I intend to demonstrate and analyse the material workings…

Stories and the Development of Virtue

ERIC Educational Resources Information Center

Willows, Adam M.

2017-01-01

From folk tales to movies, stories possess features which naturally suit them to contribute to the growth of virtue. In this article I show that the fictional exemplars help the learner to grasp the moral importance of internal states and resolves a tension between existing kinds of exemplars discussed by virtue ethicists. Stories also increase…

Tales and Visions of the Korean War: A Guide to Internet Resources.

ERIC Educational Resources Information Center

Redstone, Victoria

2000-01-01

Provides an annotated list of Internet resources featuring lesson plans, background information, and documents pertaining to the Korean War. Highlights topics such as, but not limited to, the division of North and South Korea, a U.S. civilian massacre during the war, and a North Korean's memoir. (CMK)

Playing in the Dark with Online Games for Girls

ERIC Educational Resources Information Center

Sinker, Rebecca; Phillips, Mike; de Rijke, Victoria

2017-01-01

"Pregnant Rapunzel Emergency" is part of a series of online free games aimed at young girls (forhergames.com or babygirlgames.com), where dozens of characters from fairy tales, children's toys and media feature in recovery settings, such as "Barbie flu". The range of games available to choose from includes not only dressing,…

ICT Support for Collaborative Learning--A Tale of Two Cities

ERIC Educational Resources Information Center

Consiglio, Teresa; van der Veer, Gerrit C.

2013-01-01

Based on experiences in teaching service design in a blended learning context, we developed an electronic learning environment (ELE) including features that turned out to be suitable for learners from different cultures. We used this ELE in Italy and in China. Students were guided through collaborative learning and mutual teaching. Students were…

Gender Transformations and Colonial Displacements in Laura Antillano's "Tuna de mar"

ERIC Educational Resources Information Center

Reid, Alana

2015-01-01

This paper examines the trajectories of two characters in Laura Antillano's short story, "Tuna de mar" (1991), as they navigate interrelated systems of power and attempt to position themselves closer to, or further away from, the margins. Set in the late eighteenth century, the tale features a female protagonist who escapes prostitution…

A Fairy-Tale Landscape

NASA Technical Reports Server (NTRS)

2008-01-01

[figure removed for brevity, see original site] Click on image for animation

Fun, fairy-tale nicknames have been assigned to features in this animated view of the workspace reachable by the robotic arm of NASA's Phoenix Mars Lander. For example, 'Sleepy Hollow' denotes a trench and 'Headless' designates a rock.

A 'National Park,' marked by purple text and a purple arrow, has been set aside for protection until scientists and engineers have tested the operation of the robotic scoop. First touches with the scoop will be to the left of the 'National Park' line.

Scientists use such informal names for easy identification of features of interest during the mission.

In this view, rocks are circled in yellow, other areas of interest in green. The images were taken by the lander's 7-foot mast camera, called the Surface Stereo Imager.

The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

DNA-binding proteins from marine bacteria expand the known sequence diversity of TALE-like repeats

PubMed Central

de Lange, Orlando; Wolf, Christina; Thiel, Philipp; Krüger, Jens; Kleusch, Christian; Kohlbacher, Oliver; Lahaye, Thomas

2015-01-01

Transcription Activator-Like Effectors (TALEs) of Xanthomonas bacteria are programmable DNA binding proteins with unprecedented target specificity. Comparative studies into TALE repeat structure and function are hindered by the limited sequence variation among TALE repeats. More sequence-diverse TALE-like proteins are known from Ralstonia solanacearum (RipTALs) and Burkholderia rhizoxinica (Bats), but RipTAL and Bat repeats are conserved with those of TALEs around the DNA-binding residue. We study two novel marine-organism TALE-like proteins (MOrTL1 and MOrTL2), the first to date of non-terrestrial origin. We have assessed their DNA-binding properties and modelled repeat structures. We found that repeats from these proteins mediate sequence specific DNA binding conforming to the TALE code, despite low sequence similarity to TALE repeats, and with novel residues around the BSR. However, MOrTL1 repeats show greater sequence discriminating power than MOrTL2 repeats. Sequence alignments show that there are only three residues conserved between repeats of all TALE-like proteins including the two new additions. This conserved motif could prove useful as an identifier for future TALE-likes. Additionally, comparing MOrTL repeats with those of other TALE-likes suggests a common evolutionary origin for the TALEs, RipTALs and Bats. PMID:26481363

Medical cost analysis: application to colorectal cancer data from the SEER Medicare database.

PubMed

Bang, Heejung

2005-10-01

Incompleteness is a key feature of most survival data. Numerous well established statistical methodologies and algorithms exist for analyzing life or failure time data. However, induced censorship invalidates the use of those standard analytic tools for some survival-type data such as medical costs. In this paper, some valid methods currently available for analyzing censored medical cost data are reviewed. Some cautionary findings under different assumptions are envisioned through application to medical costs from colorectal cancer patients. Cost analysis should be suitably planned and carefully interpreted under various meaningful scenarios even with judiciously selected statistical methods. This approach would be greatly helpful to policy makers who seek to prioritize health care expenditures and to assess the elements of resource use.

Crowdsourcing contest dilemma

PubMed Central

Naroditskiy, Victor; Jennings, Nicholas R.; Van Hentenryck, Pascal; Cebrian, Manuel

2014-01-01

Crowdsourcing offers unprecedented potential for solving tasks efficiently by tapping into the skills of large groups of people. A salient feature of crowdsourcing—its openness of entry—makes it vulnerable to malicious behaviour. Such behaviour took place in a number of recent popular crowdsourcing competitions. We provide game-theoretic analysis of a fundamental trade-off between the potential for increased productivity and the possibility of being set back by malicious behaviour. Our results show that in crowdsourcing competitions malicious behaviour is the norm, not the anomaly—a result contrary to the conventional wisdom in the area. Counterintuitively, making the attacks more costly does not deter them but leads to a less desirable outcome. These findings have cautionary implications for the design of crowdsourcing competitions. PMID:25142518

DNA-binding proteins from marine bacteria expand the known sequence diversity of TALE-like repeats.

PubMed

de Lange, Orlando; Wolf, Christina; Thiel, Philipp; Krüger, Jens; Kleusch, Christian; Kohlbacher, Oliver; Lahaye, Thomas

2015-11-16

Transcription Activator-Like Effectors (TALEs) of Xanthomonas bacteria are programmable DNA binding proteins with unprecedented target specificity. Comparative studies into TALE repeat structure and function are hindered by the limited sequence variation among TALE repeats. More sequence-diverse TALE-like proteins are known from Ralstonia solanacearum (RipTALs) and Burkholderia rhizoxinica (Bats), but RipTAL and Bat repeats are conserved with those of TALEs around the DNA-binding residue. We study two novel marine-organism TALE-like proteins (MOrTL1 and MOrTL2), the first to date of non-terrestrial origin. We have assessed their DNA-binding properties and modelled repeat structures. We found that repeats from these proteins mediate sequence specific DNA binding conforming to the TALE code, despite low sequence similarity to TALE repeats, and with novel residues around the BSR. However, MOrTL1 repeats show greater sequence discriminating power than MOrTL2 repeats. Sequence alignments show that there are only three residues conserved between repeats of all TALE-like proteins including the two new additions. This conserved motif could prove useful as an identifier for future TALE-likes. Additionally, comparing MOrTL repeats with those of other TALE-likes suggests a common evolutionary origin for the TALEs, RipTALs and Bats. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Exploring Mechanisms of Effective Teacher Coaching: A Tale of Two Cohorts From a Randomized Experiment

ERIC Educational Resources Information Center

Blazar, David; Kraft, Matthew A.

2015-01-01

Although previous research has shown that teacher coaching can improve teaching practices and student achievement, little is known about specific features of effective coaching programs. We estimate the impact of MATCH Teacher Coaching (MTC) on a range of teacher practices using a blocked randomized trial and explore how changes in the coaching…

A Southern University Embraces a Sacred Japanese Tradition

ERIC Educational Resources Information Center

Carlson, Scott

2008-01-01

This article features the reconstitution of the Place of Peace, a Buddhist temple disassembled in Japan, shipped in four containers across the Pacific Ocean, and reassembled in Furman University campus in South Carolina. How Furman decided to take on the project is an unusual tale. The temple once belonged to the Tsuzuki family, which owned and…

A Transcription Activator-Like Effector (TALE) Toolbox for Genome Engineering

PubMed Central

Sanjana, Neville E.; Cong, Le; Zhou, Yang; Cunniff, Margaret M.; Feng, Guoping; Zhang, Feng

2013-01-01

Transcription activator-like effectors (TALEs) are a class of naturally occurring DNA binding proteins found in the plant pathogen Xanthomonas sp. The DNA binding domain of each TALE consists of tandem 34-amino acid repeat modules that can be rearranged according to a simple cipher to target new DNA sequences. Customized TALEs can be used for a wide variety of genome engineering applications, including transcriptional modulation and genome editing. Here we describe a toolbox for rapid construction of custom TALE transcription factors (TALE-TFs) and nucleases (TALENs) using a hierarchical ligation procedure. This toolbox facilitates affordable and rapid construction of custom TALE-TFs and TALENs within one week and can be easily scaled up to construct TALEs for multiple targets in parallel. We also provide details for testing the activity in mammalian cells of custom TALE-TFs and TALENs using, respectively, qRT-PCR and Surveyor nuclease. The TALE toolbox described here will enable a broad range of biological applications. PMID:22222791

TALE: a tale of genome editing.

PubMed

Zhang, Mingjie; Wang, Feng; Li, Shifei; Wang, Yan; Bai, Yun; Xu, Xueqing

2014-01-01

Transcription activator-like effectors (TALEs), first identified in Xanthomonas bacteria, are naturally occurring or artificially designed proteins that modulate gene transcription. These proteins recognize and bind DNA sequences based on a variable numbers of tandem repeats. Each repeat is comprised of a set of ∼ 34 conserved amino acids; within this conserved domain, there are usually two amino acids that distinguish one TALE from another. Interestingly, TALEs have revealed a simple cipher for the one-to-one recognition of proteins for DNA bases. Synthetic TALEs have been used to successfully target genes in a variety of species, including humans. Depending on the type of functional domain that is fused to the TALE of interest, these proteins can have diverse biological effects. For example, after binding DNA, TALEs fused to transcriptional activation domains can function as robust transcription factors (TALE-TFs), while fused to restriction endonucleases (TALENs) can cut DNA. Targeted genome editing, in theory, is capable of modifying any endogenous gene sequence of interest; this can be performed in cells or organisms, and may be applied to clinical gene-based therapies in the future. With current technologies, highly accurate, specific, and reliable gene editing cannot be achieved. Thus, recognition and binding mechanisms governing TALE biology are currently hot research areas. In this review, we summarize the major advances in TALE technology over the past several years with a focus on the interaction between TALEs and DNA, TALE design and construction, potential applications for this technology, and unique characteristics that make TALEs superior to zinc finger endonucleases. Copyright © 2013 Elsevier Ltd. All rights reserved.

Direct observation of TALE protein dynamics reveals a two-state search mechanism

PubMed Central

Cuculis, Luke; Abil, Zhanar; Zhao, Huimin; Schroeder, Charles M.

2015-01-01

Transcription activator-like effector (TALE) proteins are a class of programmable DNA-binding proteins for which the fundamental mechanisms governing the search process are not fully understood. Here we use single-molecule techniques to directly observe TALE search dynamics along DNA templates. We find that TALE proteins are capable of rapid diffusion along DNA using a combination of sliding and hopping behaviour, which suggests that the TALE search process is governed in part by facilitated diffusion. We also observe that TALE proteins exhibit two distinct modes of action during the search process—a search state and a recognition state—facilitated by different subdomains in monomeric TALE proteins. Using TALE truncation mutants, we further demonstrate that the N-terminal region of TALEs is required for the initial non-specific binding and subsequent rapid search along DNA, whereas the central repeat domain is required for transitioning into the site-specific recognition state. PMID:26027871

Direct observation of TALE protein dynamics reveals a two-state search mechanism.

PubMed

Cuculis, Luke; Abil, Zhanar; Zhao, Huimin; Schroeder, Charles M

2015-06-01

Transcription activator-like effector (TALE) proteins are a class of programmable DNA-binding proteins for which the fundamental mechanisms governing the search process are not fully understood. Here we use single-molecule techniques to directly observe TALE search dynamics along DNA templates. We find that TALE proteins are capable of rapid diffusion along DNA using a combination of sliding and hopping behaviour, which suggests that the TALE search process is governed in part by facilitated diffusion. We also observe that TALE proteins exhibit two distinct modes of action during the search process-a search state and a recognition state-facilitated by different subdomains in monomeric TALE proteins. Using TALE truncation mutants, we further demonstrate that the N-terminal region of TALEs is required for the initial non-specific binding and subsequent rapid search along DNA, whereas the central repeat domain is required for transitioning into the site-specific recognition state.

An Improved Method for TAL Effectors DNA-Binding Sites Prediction Reveals Functional Convergence in TAL Repertoires of Xanthomonas oryzae Strains

PubMed Central

Pérez-Quintero, Alvaro L.; Rodriguez-R, Luis M.; Dereeper, Alexis; López, Camilo; Koebnik, Ralf; Szurek, Boris; Cunnac, Sebastien

2013-01-01

Transcription Activators-Like Effectors (TALEs) belong to a family of virulence proteins from the Xanthomonas genus of bacterial plant pathogens that are translocated into the plant cell. In the nucleus, TALEs act as transcription factors inducing the expression of susceptibility genes. A code for TALE-DNA binding specificity and high-resolution three-dimensional structures of TALE-DNA complexes were recently reported. Accurate prediction of TAL Effector Binding Elements (EBEs) is essential to elucidate the biological functions of the many sequenced TALEs as well as for robust design of artificial TALE DNA-binding domains in biotechnological applications. In this work a program with improved EBE prediction performances was developed using an updated specificity matrix and a position weight correction function to account for the matching pattern observed in a validation set of TALE-DNA interactions. To gain a systems perspective on the large TALE repertoires from X. oryzae strains, this program was used to predict rice gene targets for 99 sequenced family members. Integrating predictions and available expression data in a TALE-gene network revealed multiple candidate transcriptional targets for many TALEs as well as several possible instances of functional convergence among TALEs. PMID:23869221

Engineering customized TALE nucleases (TALENs) and TALE transcription factors by fast ligation-based automatable solid-phase high-throughput (FLASH) assembly.

PubMed

Reyon, Deepak; Maeder, Morgan L; Khayter, Cyd; Tsai, Shengdar Q; Foley, Jonathan E; Sander, Jeffry D; Joung, J Keith

2013-07-01

Customized DNA-binding domains made using transcription activator-like effector (TALE) repeats are rapidly growing in importance as widely applicable research tools. TALE nucleases (TALENs), composed of an engineered array of TALE repeats fused to the FokI nuclease domain, have been used successfully for directed genome editing in various organisms and cell types. TALE transcription factors (TALE-TFs), consisting of engineered TALE repeat arrays linked to a transcriptional regulatory domain, have been used to up- or downregulate expression of endogenous genes in human cells and plants. This unit describes a detailed protocol for the recently described fast ligation-based automatable solid-phase high-throughput (FLASH) assembly method. FLASH enables automated high-throughput construction of engineered TALE repeats using an automated liquid handling robot or manually using a multichannel pipet. Using the automated approach, a single researcher can construct up to 96 DNA fragments encoding TALE repeat arrays of various lengths in a single day, and then clone these to construct sequence-verified TALEN or TALE-TF expression plasmids in a week or less. Plasmids required for FLASH are available by request from the Joung lab (http://eGenome.org). This unit also describes improvements to the Zinc Finger and TALE Targeter (ZiFiT Targeter) web server (http://ZiFiT.partners.org) that facilitate the design and construction of FLASH TALE repeat arrays in high throughput. © 2013 by John Wiley & Sons, Inc.

Engineering Customized TALE Nucleases (TALENs) and TALE Transcription Factors by Fast Ligation-based Automatable Solid-phase High-throughput (FLASH) Assembly

PubMed Central

Reyon, Deepak; Maeder, Morgan L.; Khayter, Cyd; Tsai, Shengdar Q.; Foley, Jonathan E.; Sander, Jeffry D.; Joung, J. Keith

2013-01-01

Customized DNA-binding domains made using Transcription Activator-Like Effector (TALE) repeats are rapidly growing in importance as widely applicable research tools. TALE nucleases (TALENs), composed of an engineered array of TALE repeats fused to the FokI nuclease domain, have been used successfully for directed genome editing in multiple different organisms and cell types. TALE transcription factors (TALE-TFs), consisting of engineered TALE repeat arrays linked to a transcriptional regulatory domain, have been used to up- or down-regulate expression of endogenous genes in human cells and plants. Here we describe a detailed protocol for practicing the recently described Fast Ligation-based Automatable Solid-phase High-throughput (FLASH) assembly method. FLASH enables automated high-throughput construction of engineered TALE repeats using an automated liquid handling robot or manually using a multi-channel pipet. With the automated version of FLASH, a single researcher can construct up to 96 DNA fragments encoding various length TALE repeat arrays in one day and then clone these to construct sequence-verified TALEN or TALE-TF expression plasmids in one week or less. Plas-mids required to practice FLASH are available by request from the Joung Lab (http://www.jounglab.org/). We also describe here improvements to the Zinc Finger and TALE Targeter (ZiFiT Targeter) webserver (http://ZiFiTBeta.partners.org) that facilitate the design and construction of FLASH TALE repeat arrays in high-throughput. PMID:23821439

Cullen, a Cautionary Tale

PubMed Central

Dyde, Sean

2015-01-01

Some ideas return after the briefest of exiles: reductionism is back in vogue. Existential questions – about who we are, about our origins and future, about what is valuable – no longer require difficult soul searching, especially when straightforward answers are expected from the neurosciences. History is being rewritten with the brain as its centrepiece; the search for great men and big ideas of the past begins again. William Cullen (1710–90), whose work on neurosis was once part of the history of psychoanalysis, is now well placed to become part of such a neuro-history. This article attempts to subvert this process, by rebuilding the original meaning of neurosis through Cullen’s physiological and medical works, in comparison with his predecessor, Robert Whytt (1714–66), and illustrating this meaning using one particular neurosis: hypochondriasis. The result is a more complicated version of neurosis which, importantly, carries significant insights into the nature and practice of medicine. Moreover, this article examines how Cullen’s standing fell in the 1820s as British physicians and surgeons turned to an idea which promised to reform medicine: pathological anatomy. When these hopes faded, Cullen became a figure obsessed with the nerves. This image has survived to the present, a blank canvas onto which any theory can be projected. It also values precisely what Cullen warned against: simplistic explanations of the body and disease, and unthinking confidence in the next big idea or silver bullet. Neurosis was not simply a nervous ailment, but it is a warning against reductionism in history making. PMID:25766541

Oral language skills intervention in pre-school-a cautionary tale.

PubMed

Haley, Allyson; Hulme, Charles; Bowyer-Crane, Claudine; Snowling, Margaret J; Fricke, Silke

2017-01-01

While practitioners are increasingly asked to be mindful of the evidence base of intervention programmes, evidence from rigorous trials for the effectiveness of interventions that promote oral language abilities in the early years is sparse. To evaluate the effectiveness of a language intervention programme for children identified as having poor oral language skills in preschool classes. A randomized controlled trial was carried out in 13 UK nursery schools. In each nursery, eight children (N = 104, mean age = 3 years 11 months) with the poorest performance on standardized language measures were selected to take part. All but one child were randomly allocated to either an intervention (N = 52) or a waiting control group (N = 51). The intervention group received a 15-week oral language programme in addition to their standard nursery curriculum. The programme was delivered by trained teaching assistants and aimed to foster vocabulary knowledge, narrative and listening skills. Initial results revealed significant differences between the intervention and control group on measures of taught vocabulary. No group differences were found on any standardized language measure; however, there were gains of moderate effect size in listening comprehension. The study suggests that an intervention, of moderate duration and intensity, for small groups of preschool children successfully builds vocabulary knowledge, but does not generalize to non-taught areas of language. The findings strike a note of caution about implementing language interventions of moderate duration in preschool settings. The findings also highlight the importance of including a control group in intervention studies. © 2016 Royal College of Speech and Language Therapists.

Power Imbalances, Food Insecurity, and Children's Rights in Canada.

PubMed

Blay-Palmer, Alison

2016-01-01

Increasingly, food is provided through an industrial food system that separates people from the source of their food and results in high rates of food insecurity, particularly for the most vulnerable in society. A lack of food is a symptom of a lack of power in a system that privileges free market principles over social justice and the protection of human rights. In Canada, the high rates of food insecurity among Canadian children is a reflection of their lack of power and the disregard of their human rights, despite the adoption of the United Nations (UN) Convention on the Rights of the Child in 1991 and ratification of the International Covenant on Social, Economic and Cultural Rights in 1976, which established the right to food for all Canadians. Dueling tensions between human rights and market forces underpin this unacceptable state of affairs in Canada. Gaventa's "power cube" that describes different facets of power - including spaces, levels, and forms - is used to help understand the power imbalances that underlie this injustice. The analysis considers the impact of neoliberal free market principles on the realization of human rights, and the negative impacts this can have on health and well-being for the most vulnerable in society. Canadian case studies from both community organizations provide examples of how power can be shifted to achieve more inclusive, rights-based policy and action. Given increased global pressures toward more open trade markets and national austerity measures that hollow out social supports, Canada provides a cautionary tale for countries in the EU and the US, and for overall approaches to protect the most vulnerable in society.

Within and between Population Variation in Epidermal Club Cell Investment in a Freshwater Prey Fish: A Cautionary Tale for Evolutionary Ecologists

PubMed Central

Manek, Aditya K.; Ferrari, Maud C. O.; Pollock, Robyn J.; Vicente, Daniel; Weber, Lynn P.; Chivers, Douglas P.

2013-01-01

Many prey fishes possess large club cells in their epidermis. The role of these cells has garnered considerable attention from evolutionary ecologists. These cells likely form part of the innate immune system of fishes, however, they also have an alarm function, releasing chemical cues that serve to warn nearby conspecifics of danger. Experiments aimed at understanding the selection pressures leading to the evolution of these cells have been hampered by a surprisingly large intraspecific variation in epidermal club cell (ECC) investment. The goal of our current work was to explore the magnitude and nature of this variation in ECC investment. In a field survey, we documented large differences in ECC investment both within and between several populations of minnows. We then tested whether we could experimentally reduce variation in mean ECC number by raising fish under standard laboratory conditions for 4 weeks. Fish from different populations responded very differently to being held under standard laboratory conditions; some populations showed an increase in ECC investment while others remained unchanged. More importantly, we found some evidence that we could reduce within population variation in ECC investment through time, but could not reduce among-population variation in mean ECC investment. Given the large variation we observed in wild fish and our limited ability to converge mean cell number by holding the fish under standard conditions, we caution that future studies may be hard pressed to find subtle effects of various experimental manipulations; this will make elucidating the selection pressures leading to the evolution of the cells challenging. PMID:23469175

Unreliability as a Threat to Understanding Psychopathology: The Cautionary Tale of Attentional Bias

PubMed Central

Rodebaugh, Thomas L.; Scullin, Rachel B.; Langer, Julia K.; Dixon, David J.; Huppert, Jonathan D.; Bernstein, Amit; Zvielli, Ariel; Lenze, Eric J.

2016-01-01

The use of unreliable measures constitutes a threat to our understanding of psychopathology, because advancement of science using both behavioral and biologically-oriented measures can only be certain if such measurements are reliable. Two pillars of NIMH’s portfolio – the Research Domain Criteria (RDoC) initiative for psychopathology and the target engagement initiative in clinical trials – cannot succeed without measures that possess the high reliability necessary for tests involving mediation and selection based on individual differences. We focus on the historical lack of reliability of attentional bias measures as an illustration of how reliability can pose a threat to our understanding. Our own data replicate previous findings of poor reliability for traditionally-used scores, which suggests a serious problem with the ability to test theories regarding attentional bias. This lack of reliability may also suggest problems with the assumption (in both theory and the formula for the scores) that attentional bias is consistent and stable across time. In contrast, measures accounting for attention as a dynamic process in time show good reliability in our data. The field is sorely in need of research reporting findings and reliability for attentional bias scores using multiple methods, including those focusing on dynamic processes over time. We urge researchers to test and report reliability of all measures, considering findings of low reliability not just as a nuisance but as an opportunity to modify and improve upon the underlying theory. Full assessment of reliability of measures will maximize the possibility that RDoC (and psychological science more generally) will succeed. PMID:27322741

Space Geoengineering: James A. Van Allen's Role in Detecting and Disrupting the Magnetosphere, 1958-1962 (Invited)

NASA Astrophysics Data System (ADS)

Fleming, J. R.

2010-12-01

James A. Van Allen’s celebrated discovery of Earth’s radiation belts in 1958 using Explorer 1 and 3 satellites was immediately followed by his agreement to monitor tests of nuclear weapons in space aimed at disrupting the magnetosphere. This is “space geoengineering” on a planetary scale. “Space is radioactive,” noted Van Allen’s colleague Eric Ray, and the military wanted to make it even more radioactive by nuclear detonations that, in time of war might disrupt enemy radio communications from half a world away and damage or destroy enemy intercontinental ballistic missiles. This study of Van Allen’s participation in Project Argus (1958) and Project Starfish (1962) is based on new posthumous accessions to the Van Allen Papers. At the time radio astronomers protested that, “No government has the right to change the environment in any significant way without prior international study and agreement.” Van Allen later regretted his participation in experiments that disrupted the natural magnetosphere. In a larger policy framework, the history of these space interventions and the protests they generated serve as a cautionary tale for today’s geoengineers who are proposing heavy-handed manipulation of the planetary environment as a response to future climate warming. Anyone claiming that geoengineering has not yet been attempted should be reminded of the planetary-scale engineering of these nukes in space. N. Christofilos describing the intended effect of the Argus nuclear explosions on the magnetosphere, which would direct a stream of radioactive particles along magnetic lines of force half a world away.

Beacon of Hope? Lessons Learned from Efforts to Reduce Civilian Deaths from Police Shootings in an Australian State.

PubMed

Saligari, Jessica; Evans, Richard

2016-04-01

In the 1990s, the police service in Victoria, Australia, faced a crisis of community confidence due to a spate of civilian deaths from police shootings. In that decade, twice as many civilians died at the hands of the police in Victoria than in every other Australian state combined. Most of those killed were mentally ill and affected by drugs and alcohol, and were rarely a serious threat except to themselves. The problem was also almost entirely an urban phenomenon. Shootings in rural communities, where mentally ill people were more likely to be personally known to local police, were (and remain) almost unknown. The large number of fatalities was recognised as a serious threat to public confidence, and Victoria Police introduced a ground-breaking training programme, Operation Beacon. Operating procedures and weapons training were fundamentally changed, to focus on de-escalation of conflict and avoiding or minimising police use of force. In the short term, Operation Beacon was successful. Shooting incidents were dramatically reduced. However, during the first decade of the new century, the number of civilians being killed again increased. This article examines Operation Beacon, both as a successful model for reducing civilian deaths at the hand of police and as a cautionary tale for police reform. We argue that the lessons of Operation Beacon have been gradually forgotten and that old habits and attitudes resurfaced. Fatal shootings of mentally ill civilians can be prevented, but if success is to be other than temporary, the Beacon philosophy must be continually reemphasised by police management.

Prunus africana (Hook.f.) Kalkman: The Overexploitation of a Medicinal Plant Species and Its Legal Context

PubMed Central

Bodeker, Gerard; Weisbord, Emma

2014-01-01

Abstract The linkage between herbal medicines and the sustainability of medical plants from which they are manufactured is increasingly being understood and receiving attention through international accords and trade labeling systems. However, little attention is paid to the fair trade aspects of this sector, including the issue of benefit-sharing agreements with traditional societies whose knowledge and resources are being exploited for commercial herbal medicine development and production. This article examines the case of Prunus africana (Hook.f.) Kalkman, from equatorial Africa. While the conservation and cultivation dimension of the trade in P. africana has been much discussed in literature, no research appears to have focused on the traditional resource rights and related ethical dimensions of this trade in traditional medicine of Africa. Serving as a cautionary tale for the unbridled exploitation of medicinal plants, the history of P. africana extraction is considered here in the context of relevant treaties and agreements existing today. These include the Nagoya Protocol, a supplementary agreement to the Convention on Biological Diversity, the Trade-Related Aspects of Intellectual Property Rights agreement from the World Trade Organization, and two African regional frameworks: the Swakopmund Protocol and the Organisation Africaine de la Propriété Intellectuelle Initiative. In the context of strengthening medicinal plant research in Africa, a novel international capacity-building project on traditional medicines for better public health in Africa will be discussed, illustrating how access and benefit sharing principles might be incorporated in future projects on traditional medicines. PMID:25225776

Gene expression profile differences in left and right liver lobes from mid-gestation fetal baboons: a cautionary tale

PubMed Central

Cox, Laura A; Schlabritz-Loutsevitch, Natalia; Hubbard, Gene B; Nijland, Mark J; McDonald, Thomas J; Nathanielsz, Peter W

2006-01-01

Interpretation of gene array data presents many potential pitfalls in adult tissues. Gene array techniques applied to fetal tissues present additional confounding pitfalls. The left lobe of the fetal liver is supplied with blood containing more oxygen than the right lobe. Since synthetic activity and cell function are oxygen dependent, we hypothesized major differences in mRNA expression between the fetal right and left liver lobes. Our aim was to demonstrate the need to evaluate RNA samples from both lobes. We performed whole genome expression profiling on left and right liver lobe RNA from six 90-day gestation baboon fetuses (term 180 days). Comparing right with left, we found 875 differentially expressed genes – 312 genes were up-regulated and 563 down-regulated. Pathways for damaged DNA binding, endonuclease activity, interleukin binding and receptor activity were up-regulated in right lobe; ontological pathways related to cell signalling, cell organization, cell biogenesis, development, intracellular transport, phospholipid metabolism, protein biosynthesis, protein localization, protein metabolism, translational regulation and vesicle mediated transport were down-regulated in right lobe. Molecular pathway analysis showed down-regulation of pathways related to heat shock protein binding, ion channel and transporter activities, oxygen binding and transporter activities, translation initiation and translation regulator activities. Genes involved in amino acid biosynthesis, lipid biosynthesis and oxygen transport were also differentially expressed. This is the first demonstration of RNA differences between the two lobes of the fetal liver. The data support the argument that a complete interpretation of gene expression in the developing liver requires data from both lobes. PMID:16484296

Intronic deletions in the SLC34A3 gene: A cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria

PubMed Central

Ichikawa, Shoji; Tuchman, Shamir; Padgett, Leah R.; Gray, Amie K.; Baluarte, H. Jorge; Econs, Michael J.

2013-01-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare metabolic disorder, characterized by hypophosphatemia, variable degrees of rickets/osteomalacia, and hypercalciuria secondary to increased serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels. HHRH is caused by mutations in the SLC34A3 gene, which encodes sodium-phosphate co-transporter type IIc. A 6 ½-year-old female presented with a history of nephrolithiasis. Her metabolic evaluation revealed increased 24- hour urine calcium excretion with high serum calcium, low intact parathyroid hormone (PTH) levels, and elevated 1,25(OH)2D level. In addition, the patient had low to low-normal serum phosphorus with high urine phosphorus. The patient had normal stature; without rachitic or boney deformities or a history of fractures. Genetic analysis of SLC34A3 revealed the patient to be a compound heterozygote for a novel single base pair deletion in exon 12 (c.1304delG) and 30-base pair deletion in intron 6 (g.1440–1469del). The single-base pair mutation causes a frameshift, which results in premature stop codon. The intronic deletion is likely caused by misalignment of the 4-basepair homologous repeats and results in the truncation of an already small intron to 63 bp, which would impair proper RNA splicing of the intron. This is the fourth unique intronic deletion identified in patients with HHRH, suggesting the frequent occurrence of sequence misalignments in SLC34A3 and the importance of screening introns in patients with HHRH. PMID:24176905

Intronic deletions in the SLC34A3 gene: a cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria.

PubMed

Ichikawa, Shoji; Tuchman, Shamir; Padgett, Leah R; Gray, Amie K; Baluarte, H Jorge; Econs, Michael J

2014-02-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare metabolic disorder, characterized by hypophosphatemia, variable degrees of rickets/osteomalacia, and hypercalciuria secondary to increased serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels. HHRH is caused by mutations in the SLC34A3 gene, which encodes sodium-phosphate co-transporter type IIc. A 6-1/2-year-old female presented with a history of nephrolithiasis. Her metabolic evaluation revealed increased 24-hour urine calcium excretion with high serum calcium, low intact parathyroid hormone (PTH), and elevated 1,25(OH)2D. In addition, the patient had low to low-normal serum phosphorus with high urine phosphorus. The patient had normal stature; without rachitic or boney deformities or a history of fractures. Genetic analysis of SLC34A3 revealed the patient to be a compound heterozygote for a novel single base pair deletion in exon 12 (c.1304delG) and 30-base pair deletion in intron 6 (g.1440-1469del). The single-base pair mutation causes a frameshift, which results in premature stop codon. The intronic deletion is likely caused by misalignment of the 4-basepair homologous repeats and results in the truncation of an already small intron to 63bp, which would impair proper RNA splicing of the intron. This is the fourth unique intronic deletion identified in patients with HHRH, suggesting the frequent occurrence of sequence misalignments in SLC34A3 and the importance of screening introns in patients with HHRH. © 2013.

Diversity of introduced terrestrial flatworms in the Iberian Peninsula: a cautionary tale

PubMed Central

Álvarez-Presas, Marta; Tudó, Àngels; Jones, Hugh; Riutort, Marta

2014-01-01

Many tropical terrestrial planarians (Platyhelminthes, Geoplanidae) have been introduced around the globe. One of these species is known to cause significant decline in earthworm populations, resulting in a reduction of ecological functions that earthworms provide. Flatworms, additionally, are a potential risk to other species that have the same dietary needs. Hence, the planarian invasion might cause significant economic losses in agriculture and damage to the ecosystem. In the Iberian Peninsula only Bipalium kewense Moseley, 1878 had been cited till 2007. From that year on, four more species have been cited, and several reports of the presence of these animals in particular gardens have been received. In the present study we have: (1) analyzed the animals sent by non-specialists and also the presence of terrestrial planarians in plant nurseries and garden centers; (2) identified their species through morphological and phylogenetic molecular analyses, including representatives of their areas of origin; (3) revised their dietary sources and (4) used Species Distribution Modeling (SDM) for one species to evaluate the risk of its introduction to natural areas. The results have shown the presence of at least ten species of alien terrestrial planarians, from all its phylogenetic range. International plant trade is the source of these animals, and many garden centers are acting as reservoirs. Also, landscape restoration to reintroduce autochthonous plants has facilitated their introduction close to natural forests and agricultural fields. In conclusion, there is a need to take measures on plant trade and to have special care in the treatment of restored habitats. PMID:24949245

No Evidence That Schizophrenia Candidate Genes Are More Associated With Schizophrenia Than Noncandidate Genes.

PubMed

Johnson, Emma C; Border, Richard; Melroy-Greif, Whitney E; de Leeuw, Christiaan A; Ehringer, Marissa A; Keller, Matthew C

2017-11-15

A recent analysis of 25 historical candidate gene polymorphisms for schizophrenia in the largest genome-wide association study conducted to date suggested that these commonly studied variants were no more associated with the disorder than would be expected by chance. However, the same study identified other variants within those candidate genes that demonstrated genome-wide significant associations with schizophrenia. As such, it is possible that variants within historic schizophrenia candidate genes are associated with schizophrenia at levels above those expected by chance, even if the most-studied specific polymorphisms are not. The present study used association statistics from the largest schizophrenia genome-wide association study conducted to date as input to a gene set analysis to investigate whether variants within schizophrenia candidate genes are enriched for association with schizophrenia. As a group, variants in the most-studied candidate genes were no more associated with schizophrenia than were variants in control sets of noncandidate genes. While a small subset of candidate genes did appear to be significantly associated with schizophrenia, these genes were not particularly noteworthy given the large number of more strongly associated noncandidate genes. The history of schizophrenia research should serve as a cautionary tale to candidate gene investigators examining other phenotypes: our findings indicate that the most investigated candidate gene hypotheses of schizophrenia are not well supported by genome-wide association studies, and it is likely that this will be the case for other complex traits as well. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Airline Safety Improvement Through Experience with Near-Misses: A Cautionary Tale.

PubMed

Madsen, Peter; Dillon, Robin L; Tinsley, Catherine H

2016-05-01

In recent years, the U.S. commercial airline industry has achieved unprecedented levels of safety, with the statistical risk associated with U.S. commercial aviation falling to 0.003 fatalities per 100 million passengers. But decades of research on organizational learning show that success often breeds complacency and failure inspires improvement. With accidents as rare events, can the airline industry continue safety advancements? This question is complicated by the complex system in which the industry operates where chance combinations of multiple factors contribute to what are largely probabilistic (rather than deterministic) outcomes. Thus, some apparent successes are realized because of good fortune rather than good processes, and this research intends to bring attention to these events, the near-misses. The processes that create these near-misses could pose a threat if multiple contributing factors combine in adverse ways without the intervention of good fortune. Yet, near-misses (if recognized as such) can, theoretically, offer a mechanism for continuing safety improvements, above and beyond learning gleaned from observable failure. We test whether or not this learning is apparent in the airline industry. Using data from 1990 to 2007, fixed effects Poisson regressions show that airlines learn from accidents (their own and others), and from one category of near-misses-those where the possible dangers are salient. Unfortunately, airlines do not improve following near-miss incidents when the focal event has no clear warnings of significant danger. Therefore, while airlines need to and can learn from certain near-misses, we conclude with recommendations for improving airline learning from all near-misses. © 2015 Society for Risk Analysis.

Statutory complexity disguises agency capture in Citizens Coal Council v. EPA

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

Mullen, R.

2007-07-01

In Citizens Coal Council v. EPA, an en banc panel for the Sixth Circuit Court of Appeals considered a challenge to EPA regulations promulgated pursuant to the Clean Water Act (CWA). The EPA promulgated the regulations in an attempt to incentivize coal companies to remine once abandoned mine sites. Petitioners, two nonprofit environmental organizations, claimed that the regulations violated the Clean Water Act and Administrative Procedure Act by allowing coal companies to remine without adhering to any enforceable pollution limitations. The EPA countered that more remining would improve water quality at abandoned sites. The Sixth Circuit rejected Petitioners' claims, findingmore » that the EPA's regulations were reasonably consistent with the CWA's goal of restoring the integrity of the nation's waters. In so holding, the court struggled to understand the meaning of the CWA's complex procedural and technical language, and allowed the EPA to justify the rule based on the CWA's broad statement of purpose. Such superficial judicial review sets a dangerous precedent in environmental law, because it exacerbates the risk of agency capture. A captured agency promulgates regulations that benefit-industry, not the environment. Without the judiciary acting as a meaningful check against agency capture, the public loses a valuable tool in the fight against major-industrial polluters like the domestic coal industry. Citizens Coal Council therefore stands as a cautionary tale, a warning sign that the judiciary may be unable to identify agency capture where the regulations at issue are promulgated pursuant to a complex statute like the Clean Water Act.« less

The effects of 'does not apply' on measurement of temperament with the Infant Behavior Questionnaire-Revised: A cautionary tale for very young infants.

PubMed

Giesbrecht, Gerald F; Dewey, Deborah

2014-10-01

The Infant Behavior Questionnaire-Revised (IBQ-R) is a widely used parent report measure of infant temperament. Items marked 'does not apply' (NA) are treated as missing data when calculating scale scores, but the effect of this practice on assessment of infant temperament has not been reported. To determine the effect of NA responses on assessment of infant temperament and to evaluate the remedy offered by several missing data strategies. A prospective, community-based longitudinal cohort study. 401 infants who were born>37 weeks of gestation. Mothers completed the short form of the IBQ-R when infants were 3-months and 6-months of age. The rate of NA responses at the 3-month assessment was three times as high (22%) as the rate at six months (7%). Internal consistency was appreciably reduced and scale means were inflated in the presence of NA responses, especially at 3-months. The total number of NA items endorsed by individual parents was associated with infant age and parity. None of the missing data strategies completely eliminated problems related to NA responses but the Expectation Maximization algorithm greatly reduced these problems. The findings suggest that researchers should exercise caution when interpreting results obtained from infants at 3 months of age. Careful selection of scales, selecting a full length version of the IBQ-R, and use of a modern missing data technique may help to maintain the quality of data obtained from very young infants. Copyright © 2014 Elsevier Ltd. All rights reserved.

'Thinking ill of others without sufficient warrant?' Transcending the accuracy-inaccuracy dualism in prejudice and stereotyping research.

PubMed

Dixon, John

2017-03-01

Research on prejudice seeks to understand and transform inaccurate beliefs about others. Indeed, historically such research has offered a cautionary tale of the biased nature of human cognition. Recently, however, this view has been challenged by work defending the essential rationality of intergroup perception, a theme captured controversially in Jussim and colleagues' (2009) research on the 'unbearable accuracy of stereotyping'. The present paper argues that in its own terms the 'rationalist turn' in socio-cognitive research on stereotyping presents an important challenge to the prejudice tradition, raising troubling questions about its conceptual and empirical foundations. However, it also argues for the necessity of transcending those terms. By focusing on the correspondence between individual beliefs and the supposedly 'objective' characteristics of others, we neglect the historical and discursive practices through which the social realities that we 'perceive' are actively constructed and institutionalized. We mask their social origins, contested and perspectival nature, relativity, and relationship to wider structures of power. By implication, moving beyond the Allportian perspective that has dominated both the prejudice tradition and the emerging stereotype accuracy paradigm, we may now need to prioritize other kinds of questions. Reversing Allport's famous definition of prejudice, it may now be time to ask: How, and with what consequences, does 'thinking ill of others' become sufficiently warranted? How does such thinking become part of institutionalized relations of power and an accepted way of perceiving, evaluating and treating others? What should social psychologists be doing to challenge this state of affairs? © 2017 The British Psychological Society.

Risk factor studies of age-at-onset in a sample ascertained for Parkinson disease affected sibling pairs: a cautionary tale

PubMed Central

Wilk, Jemma B; Lash, Timothy L

2007-01-01

An association between exposure to a risk factor and age-at-onset of disease may reflect an effect on the rate of disease occurrence or an acceleration of the disease process. The difference in age-at-onset arising from case-only studies, however, may also reflect secular trends in the prevalence of exposure to the risk factor. Comparisons of age-at-onset associated with risk factors are commonly performed in case series enrolled for genetic linkage analysis of late onset diseases. We describe how the results of age-at-onset studies of environmental risk factors reflect the underlying structure of the source population, rather than an association with age-at-onset, by contrasting the effects of coffee drinking and cigarette smoking on Parkinson disease age-at-onset with the effects on age-at-enrollment in a population based study sample. Despite earlier evidence to suggest a protective association of coffee drinking and cigarette smoking with Parkinson disease risk, the age-at-onset results are comparable to the patterns observed in the population sample, and thus a causal inference from the age-at-onset effect may not be justified. Protective effects of multivitamin use on PD age-at-onset are also shown to be subject to a bias from the relationship between age and multivitamin initiation. Case-only studies of age-at-onset must be performed with an appreciation for the association between risk factors and age and ageing in the source population. PMID:17408493

Deconstructing Gender in Revised Feminist Fairy Tales

ERIC Educational Resources Information Center

Mcandrew, Linda

2013-01-01

Power relationships are a central premise in children's literature, especially traditional fairy tales and modern feminist fairy tales. This is seen in many fairy tales where the main female character is in some distress, her Prince Charming rescues her, and they live happily ever after. Modern feminist fairy tales are understood to be a forum…

Lost Opportunities: Rediscovering Fairy Tales

ERIC Educational Resources Information Center

Wipf, Joan Brogan; Da Ros-Voseles, Denise

2012-01-01

The power of fairy tales resonates with children around the world. Fairy tales connect children on an emotional level that can help guide them through the complexities of everyday life. The tales provide stories rich in cultural heritage and the human condition, stories that not only delight children but also instruct. Because fairy tales state…

Design, Assembly, and Characterization of TALE-Based Transcriptional Activators and Repressors.

PubMed

Thakore, Pratiksha I; Gersbach, Charles A

2016-01-01

Transcription activator-like effectors (TALEs) are modular DNA-binding proteins that can be fused to a variety of effector domains to regulate the epigenome. Nucleotide recognition by TALE monomers follows a simple cipher, making this a powerful and versatile method to activate or repress gene expression. Described here are methods to design, assemble, and test TALE transcription factors (TALE-TFs) for control of endogenous gene expression. In this protocol, TALE arrays are constructed by Golden Gate cloning and tested for activity by transfection and quantitative RT-PCR. These methods for engineering TALE-TFs are useful for studies in reverse genetics and genomics, synthetic biology, and gene therapy.

Rapid and highly efficient construction of TALE-based transcriptional regulators and nucleases for genome modification.

PubMed

Li, Lixin; Piatek, Marek J; Atef, Ahmed; Piatek, Agnieszka; Wibowo, Anjar; Fang, Xiaoyun; Sabir, J S M; Zhu, Jian-Kang; Mahfouz, Magdy M

2012-03-01

Transcription activator-like effectors (TALEs) can be used as DNA-targeting modules by engineering their repeat domains to dictate user-selected sequence specificity. TALEs have been shown to function as site-specific transcriptional activators in a variety of cell types and organisms. TALE nucleases (TALENs), generated by fusing the FokI cleavage domain to TALE, have been used to create genomic double-strand breaks. The identity of the TALE repeat variable di-residues, their number, and their order dictate the DNA sequence specificity. Because TALE repeats are nearly identical, their assembly by cloning or even by synthesis is challenging and time consuming. Here, we report the development and use of a rapid and straightforward approach for the construction of designer TALE (dTALE) activators and nucleases with user-selected DNA target specificity. Using our plasmid set of 100 repeat modules, researchers can assemble repeat domains for any 14-nucleotide target sequence in one sequential restriction-ligation cloning step and in only 24 h. We generated several custom dTALEs and dTALENs with new target sequence specificities and validated their function by transient expression in tobacco leaves and in vitro DNA cleavage assays, respectively. Moreover, we developed a web tool, called idTALE, to facilitate the design of dTALENs and the identification of their genomic targets and potential off-targets in the genomes of several model species. Our dTALE repeat assembly approach along with the web tool idTALE will expedite genome-engineering applications in a variety of cell types and organisms including plants.

Dissection of TALE-dependent gene activation reveals that they induce transcription cooperatively and in both orientations

PubMed Central

Streubel, Jana; Baum, Heidi; Grau, Jan; Stuttman, Johannes; Boch, Jens

2017-01-01

Plant-pathogenic Xanthomonas bacteria inject transcription activator-like effector proteins (TALEs) into host cells to specifically induce transcription of plant genes and enhance susceptibility. Although the DNA-binding mode is well-understood it is still ambiguous how TALEs initiate transcription and whether additional promoter elements are needed to support this. To systematically dissect prerequisites for transcriptional initiation the activity of one TALE was compared on different synthetic Bs4 promoter fragments. In addition, a large collection of artificial TALEs spanning the OsSWEET14 promoter was compared. We show that the presence of a TALE alone is not sufficient to initiate transcription suggesting the requirement of additional supporting promoter elements. At the OsSWEET14 promoter TALEs can initiate transcription from various positions, in a synergistic manner of multiple TALEs binding in parallel to the promoter, and even by binding in reverse orientation. TALEs are known to shift the transcriptional start site, but our data show that this shift depends on the individual position of a TALE within a promoter context. Our results implicate that TALEs function like classical enhancer-binding proteins and initiate transcription in both orientations which has consequences for in planta target gene prediction and design of artificial activators. PMID:28301511

Dissection of TALE-dependent gene activation reveals that they induce transcription cooperatively and in both orientations.

PubMed

Streubel, Jana; Baum, Heidi; Grau, Jan; Stuttman, Johannes; Boch, Jens

2017-01-01

Plant-pathogenic Xanthomonas bacteria inject transcription activator-like effector proteins (TALEs) into host cells to specifically induce transcription of plant genes and enhance susceptibility. Although the DNA-binding mode is well-understood it is still ambiguous how TALEs initiate transcription and whether additional promoter elements are needed to support this. To systematically dissect prerequisites for transcriptional initiation the activity of one TALE was compared on different synthetic Bs4 promoter fragments. In addition, a large collection of artificial TALEs spanning the OsSWEET14 promoter was compared. We show that the presence of a TALE alone is not sufficient to initiate transcription suggesting the requirement of additional supporting promoter elements. At the OsSWEET14 promoter TALEs can initiate transcription from various positions, in a synergistic manner of multiple TALEs binding in parallel to the promoter, and even by binding in reverse orientation. TALEs are known to shift the transcriptional start site, but our data show that this shift depends on the individual position of a TALE within a promoter context. Our results implicate that TALEs function like classical enhancer-binding proteins and initiate transcription in both orientations which has consequences for in planta target gene prediction and design of artificial activators.

A Tale of Sea Turtles: Job-Seeking Experiences of "Hai Gui" (High-Skilled Returnees) in China

ERIC Educational Resources Information Center

Hao, Jie; Welch, Anthony

2012-01-01

A key feature of contemporary globalization is the increasing mobility of high-skilled talent. While for many countries in the developing world the loss of such individuals represents a longstanding concern, countries such as China have now developed key policies to harness their overseas talent. The article examines the job-seeking experiences of…

Edgar Allan Poe: a case description of the Marfan syndrome in an obscure short story.

PubMed

Battle, Robert W

2011-07-01

In the obscure short story “A Tale of the Ragged Mountains,” Edgar Allen Poe meticulously described a character with features remarkably consistent with the Marfan syndrome. This description appeared in fiction >50 years before the celebrated index description in the published medical research by Professor Antoine Marfan in Paris in 1896.

Learning How to Tell a Good Story: The Development of Content and Language in Children's Telling of One Tale.

ERIC Educational Resources Information Center

Stenning, Keith; Michell, Lynn

1985-01-01

Reports the results of a study showing that one stylistic feature, the inclusion of connectives other than "and/then" is a good predictor of explanation in five- to ten-year-olds, but a straightforward lack of linguistic resources is not necessarily what limits older children's achievement of explanatory narrative. (HTH)

Activation of silenced cytokine gene promoters by the synergistic effect of TBP-TALE and VP64-TALE activators.

PubMed

Anthony, Kim; More, Abhijit; Zhang, Xiaoliu

2014-01-01

Recent work has shown that the combinatorial use of multiple TALE activators can selectively activate certain cellular genes in inaccessible chromatin regions. In this study, we aimed to interrogate the activation potential of TALEs upon transcriptionally silenced immune genes in the context of non-immune cells. We designed a unique strategy, in which a single TALE fused to the TATA-box binding protein (TBP-TALE) is coupled with multiple VP64-TALE activators. We found that our strategy is significantly more potent than multiple TALE activators alone in activating expression of IL-2 and GM-CSF in diverse cell origins in which both genes are otherwise completely silenced. Chromatin analysis revealed that the gene activation was due in part to displacement of a distinctly positioned nucleosome. These studies provide a novel epigenetic mechanism for artificial gene induction and have important implications for targeted cancer immunotherapy, DNA vaccine development, as well as rational design of TALE activators.

Activation of Silenced Cytokine Gene Promoters by the Synergistic Effect of TBP-TALE and VP64-TALE Activators

PubMed Central

Anthony, Kim; More, Abhijit; Zhang, Xiaoliu

2014-01-01

Recent work has shown that the combinatorial use of multiple TALE activators can selectively activate certain cellular genes in inaccessible chromatin regions. In this study, we aimed to interrogate the activation potential of TALEs upon transcriptionally silenced immune genes in the context of non-immune cells. We designed a unique strategy, in which a single TALE fused to the TATA-box binding protein (TBP-TALE) is coupled with multiple VP64-TALE activators. We found that our strategy is significantly more potent than multiple TALE activators alone in activating expression of IL-2 and GM-CSF in diverse cell origins in which both genes are otherwise completely silenced. Chromatin analysis revealed that the gene activation was due in part to displacement of a distinctly positioned nucleosome. These studies provide a novel epigenetic mechanism for artificial gene induction and have important implications for targeted cancer immunotherapy, DNA vaccine development, as well as rational design of TALE activators. PMID:24755922

Design, Assembly, and Characterization of TALE-Based Transcriptional Activators and Repressors

PubMed Central

Thakore, Pratiksha I.; Gersbach, Charles A.

2016-01-01

Transcription activator-like effectors (TALEs) are modular DNA-binding proteins that can be fused to a variety of effector domains to regulate the epigenome. Nucleotide recognition by TALE monomers follows a simple cipher, making this a powerful and versatile method to activate or repress gene expression. Described here are methods to design, assemble, and test TALE transcription factors (TALE-TFs) for control of endogenous gene expression. In this protocol, TALE arrays are constructed by Golden Gate cloning and tested for activity by transfection and quantitative RT-PCR. These methods for engineering TALE-TFs are useful for studies in reverse genetics and genomics, synthetic biology, and gene therapy. PMID:26443215

Happily, Ever After: The Resilience of the Fairy Tale, Part 1.

ERIC Educational Resources Information Center

Hearn, Michael Patrick

1998-01-01

Discusses the work of Frenchman Charles Perrault, the seminal figure in fairy tales, and puts it in context of the French fairy tale fashion. Describes how the fairy tale came to England. Describes how the Germans revived the fairy tale at the end of the 18th century, and discusses the work of the Brothers Grimm. (SR)

TALE activators regulate gene expression in a position- and strand-dependent manner in mammalian cells.

PubMed

Uhde-Stone, Claudia; Cheung, Edna; Lu, Biao

2014-01-24

Transcription activator-like effectors (TALEs) are a class of transcription factors that are readily programmable to regulate gene expression. Despite their growing popularity, little is known about binding site parameters that influence TALE-mediated gene activation in mammalian cells. We demonstrate that TALE activators modulate gene expression in mammalian cells in a position- and strand-dependent manner. To study the effects of binding site location, we engineered TALEs customized to recognize specific DNA sequences located in either the promoter or the transcribed region of reporter genes. We found that TALE activators robustly activated reporter genes when their binding sites were located within the promoter region. In contrast, TALE activators inhibited the expression of reporter genes when their binding sites were located on the sense strand of the transcribed region. Notably, this repression was independent of the effector domain utilized, suggesting a simple blockage mechanism. We conclude that TALE activators in mammalian cells regulate genes in a position- and strand-dependent manner that is substantially different from gene activation by native TALEs in plants. These findings have implications for optimizing the design of custom TALEs for genetic manipulation in mammalian cells. Copyright © 2013 Elsevier Inc. All rights reserved.

HANSEL AND GRETEL: A TALE OF TERROR.

PubMed

White, Robert S

2015-10-01

In the analysis of a woman with multiple childhood traumas, the fairy tale "Hansel and Gretel" figured prominently. The author discusses the use of the fairy tale in this case at various levels. He suggests an interplay between a national myth, the fairy tale, and a personal myth-the patient's psychodynamics. The fairy tale can be used to illuminate personal meanings derived from it. In the experience of childhood trauma, the repeated reading of a fairy tale can help organize and defend against terrifying anxiety. © 2015 The Psychoanalytic Quarterly, Inc.

Revisiting the TALE repeat.

PubMed

Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

2014-04-01

Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

Teaching the "A" Level Text: "The Wife of Bath's Prologue and Tale."

ERIC Educational Resources Information Center

Spraggs, Gillian

1988-01-01

Presents an approach for teaching Chaucer's "Wife of Bath's Prologue and Tale" (from "The Canterbury Tales"). Recommends several reference texts related to the "The Canterbury Tales" and medieval literature in general. (MM)

The Monets, Van Goghs, and Renoirs of Science Education: Writing Impressionist Tales as a Strategy for Facilitating Prospective Teachers' Reflections on Science Experiences

NASA Astrophysics Data System (ADS)

Bryan, Lynn A.; Tippins, Deborah J.

2005-08-01

A particularly useful pedagogical strategy for beginning a dialogue with prospective teachers about the ways in which their experiences and beliefs shape their development of professional knowledge is writing impressionist tales. Impressionist tales are a form of autobiography that portrays one highly personal perspective on a significant moment in time. In this pedagogical practice article, we describe our use of impressionist tales, summarize the assumptions underpinning our use of impressionist tales in science methods courses, provide several examples of our students’ tales, and discuss the pedagogical advantages and the teacher educator’s role in using impressionist tales to promote reflective thinking among prospective elementary science teachers.

TALE factors poise promoters for activation by Hox proteins.

PubMed

Choe, Seong-Kyu; Ladam, Franck; Sagerström, Charles G

2014-01-27

Hox proteins form complexes with TALE cofactors from the Pbx and Prep/Meis families to control transcription, but it remains unclear how Hox:TALE complexes function. Examining a Hoxb1b:TALE complex that regulates zebrafish hoxb1a transcription, we find maternally deposited TALE proteins at the hoxb1a promoter already during blastula stages. These TALE factors recruit histone-modifying enzymes to promote an active chromatin profile at the hoxb1a promoter and also recruit RNA polymerase II (RNAPII) and P-TEFb. However, in the presence of TALE factors, RNAPII remains phosphorylated on serine 5 and hoxb1a transcription is inefficient. By gastrula stages, Hoxb1b binds together with TALE factors to the hoxb1a promoter. This triggers P-TEFb-mediated transitioning of RNAPII to the serine 2-phosphorylated form and efficient hoxb1a transcription. We conclude that TALE factors access promoters during early embryogenesis to poise them for activation but that Hox proteins are required to trigger efficient transcription. Copyright © 2014 Elsevier Inc. All rights reserved.

Visualization of specific repetitive genomic sequences with fluorescent TALEs in Arabidopsis thaliana

PubMed Central

Fujimoto, Satoru; Sugano, Shigeo S.; Kuwata, Keiko; Osakabe, Keishi; Matsunaga, Sachihiro

2016-01-01

Live imaging of the dynamics of nuclear organization provides the opportunity to uncover the mechanisms responsible for four-dimensional genome architecture. Here, we describe the use of fluorescent protein (FP) fusions of transcription activator-like effectors (TALEs) to visualize endogenous genomic sequences in Arabidopsis thaliana. The ability to engineer sequence-specific TALEs permits the investigation of precise genomic sequences. We could detect TALE-FP signals associated with centromeric, telomeric, and rDNA repeats and the signal distribution was consistent with that observed by fluorescent in situ hybridization. TALE-FPs are advantageous because they permit the observation of intact tissues. We used our TALE-FP method to investigate the nuclei of several multicellular plant tissues including roots, hypocotyls, leaves, and flowers. Because TALE-FPs permit live-cell imaging, we successfully observed the temporal dynamics of centromeres and telomeres in plant organs. Fusing TALEs to multimeric FPs enhanced the signal intensity when observing telomeres. We found that the mobility of telomeres was different in sub-nuclear regions. Transgenic plants stably expressing TALE-FPs will provide new insights into chromatin organization and dynamics in multicellular organisms. PMID:27811079

What Makes a Fairy Tale Good: The Queer Kindness of "The Golden Bird."

ERIC Educational Resources Information Center

Nodelman, Perry M.

1977-01-01

Uses a literary analysis of "The Golden Bird," a Grimm Brothers fairy tale, to show how an investigation of the literary qualities of fairy tales can reveal what the artistry of such tales consists of. (GT)

Engineering DNA Backbone Interactions Results in TALE Scaffolds with Enhanced 5-Methylcytosine Selectivity.

PubMed

Rathi, Preeti; Witte, Anna; Summerer, Daniel

2017-11-08

Transcription activator-like effectors (TALEs) are DNA major-groove binding proteins widely used for genome targeting. TALEs contain an N-terminal region (NTR) and a central repeat domain (CRD). Repeats of the CRD selectively recognize each one DNA nucleobase, offering programmability. Moreover, repeats with selectivity for 5-methylcytosine (5mC) and its oxidized derivatives can be designed for analytical applications. However, both TALE domains also nonspecifically interact with DNA phosphates via basic amino acids. To enhance the 5mC selectivity of TALEs, we aimed to decrease the nonselective binding energy of TALEs. We substituted basic amino acids with alanine in the NTR and identified TALE mutants with increased selectivity. We then analysed conserved, DNA phosphate-binding KQ diresidues in CRD repeats and identified further improved mutants. Combination of mutations in the NTR and CRD was highly synergetic and resulted in TALE scaffolds with up to 4.3-fold increased selectivity in genomic 5mC analysis via affinity enrichment. Moreover, transcriptional activation in HEK293T cells by a TALE-VP64 construct based on this scaffold design exhibited a 3.5-fold increased 5mC selectivity. This provides perspectives for improved 5mC analysis and for the 5mC-conditional control of TALE-based editing constructs in vivo.

Visual analysis of forest health using story maps: a tale of two forest insect pests

Treesearch

Susan J. Crocker; Brian F. Walters; Randall S. Morin

2015-01-01

Historically, results of surveys conducted by the Forest Inventory and Analysis (FIA) program of the USDA Forest Service were conveyed in printed reports, featuring text, tables and static figures. Since the advent of the Internet and with the ubiquity of mobile smart devices, technology has changed how people consume information, as well as how they experience and...

Rapid and accurate synthesis of TALE genes from synthetic oligonucleotides.

PubMed

Wang, Fenghua; Zhang, Hefei; Gao, Jingxia; Chen, Fengjiao; Chen, Sijie; Zhang, Cuizhen; Peng, Gang

2016-01-01

Custom synthesis of transcription activator-like effector (TALE) genes has relied upon plasmid libraries of pre-fabricated TALE-repeat monomers or oligomers. Here we describe a novel synthesis method that directly incorporates annealed synthetic oligonucleotides into the TALE-repeat units. Our approach utilizes iterative sets of oligonucleotides and a translational frame check strategy to ensure the high efficiency and accuracy of TALE-gene synthesis. TALE arrays of more than 20 repeats can be constructed, and the majority of the synthesized constructs have perfect sequences. In addition, this novel oligonucleotide-based method can readily accommodate design changes to the TALE repeats. We demonstrated an increased gene targeting efficiency against a genomic site containing a potentially methylated cytosine by incorporating non-conventional repeat variable di-residue (RVD) sequences.

Robust, synergistic regulation of human gene expression using TALE activators.

PubMed

Maeder, Morgan L; Linder, Samantha J; Reyon, Deepak; Angstman, James F; Fu, Yanfang; Sander, Jeffry D; Joung, J Keith

2013-03-01

Artificial activators designed using transcription activator-like effector (TALE) technology have broad utility, but previous studies suggest that these monomeric proteins often exhibit low activities. Here we demonstrate that TALE activators can robustly function individually or in synergistic combinations to increase expression of endogenous human genes over wide dynamic ranges. These findings will encourage applications of TALE activators for research and therapy, and guide design of monomeric TALE-based fusion proteins.

TALE factors use two distinct functional modes to control an essential zebrafish gene expression program.

PubMed

Ladam, Franck; Stanney, William; Donaldson, Ian J; Yildiz, Ozge; Bobola, Nicoletta; Sagerström, Charles G

2018-06-18

TALE factors are broadly expressed embryonically and known to function in complexes with transcription factors (TFs) like Hox proteins at gastrula/segmentation stages, but it is unclear if such generally expressed factors act by the same mechanism throughout embryogenesis. We identify a TALE-dependent gene regulatory network (GRN) required for anterior development and detect TALE occupancy associated with this GRN throughout embryogenesis. At blastula stages, we uncover a novel functional mode for TALE factors, where they occupy genomic DECA motifs with nearby NF-Y sites. We demonstrate that TALE and NF-Y form complexes and regulate chromatin state at genes of this GRN. At segmentation stages, GRN-associated TALE occupancy expands to include HEXA motifs near PBX:HOX sites. Hence, TALE factors control a key GRN, but utilize distinct DNA motifs and protein partners at different stages - a strategy that may also explain their oncogenic potential and may be employed by other broadly expressed TFs. © 2018, Ladam et al.

Why replication is important in landscape genetics: American black bear in the Rocky Mountains

USGS Publications Warehouse

Short, Bull R.A.; Cushman, S.A.; MacE, R.; Chilton, T.; Kendall, K.C.; Landguth, E.L.; Schwartz, Maurice L.; McKelvey, K.; Allendorf, F.W.; Luikart, G.

2011-01-01

We investigated how landscape features influence gene flow of black bears by testing the relative support for 36 alternative landscape resistance hypotheses, including isolation by distance (IBD) in each of 12 study areas in the north central U.S. Rocky Mountains. The study areas all contained the same basic elements, but differed in extent of forest fragmentation, altitude, variation in elevation and road coverage. In all but one of the study areas, isolation by landscape resistance was more supported than IBD suggesting gene flow is likely influenced by elevation, forest cover, and roads. However, the landscape features influencing gene flow varied among study areas. Using subsets of loci usually gave models with the very similar landscape features influencing gene flow as with all loci, suggesting the landscape features influencing gene flow were correctly identified. To test if the cause of the variability of supported landscape features in study areas resulted from landscape differences among study areas, we conducted a limiting factor analysis. We found that features were supported in landscape models only when the features were highly variable. This is perhaps not surprising but suggests an important cautionary note – that if landscape features are not found to influence gene flow, researchers should not automatically conclude that the features are unimportant to the species’ movement and gene flow. Failure to investigate multiple study areas that have a range of variability in landscape features could cause misleading inferences about which landscape features generally limit gene flow. This could lead to potentially erroneous identification of corridors and barriers if models are transferred between areas with different landscape characteristics.

A Simple and Efficient Method for Assembling TALE Protein Based on Plasmid Library

PubMed Central

Xu, Huarong; Xin, Ying; Zhang, Tingting; Ma, Lixia; Wang, Xin; Chen, Zhilong; Zhang, Zhiying

2013-01-01

DNA binding domain of the transcription activator-like effectors (TALEs) from Xanthomonas sp. consists of tandem repeats that can be rearranged according to a simple cipher to target new DNA sequences with high DNA-binding specificity. This technology has been successfully applied in varieties of species for genome engineering. However, assembling long TALE tandem repeats remains a big challenge precluding wide use of this technology. Although several new methodologies for efficiently assembling TALE repeats have been recently reported, all of them require either sophisticated facilities or skilled technicians to carry them out. Here, we described a simple and efficient method for generating customized TALE nucleases (TALENs) and TALE transcription factors (TALE-TFs) based on TALE repeat tetramer library. A tetramer library consisting of 256 tetramers covers all possible combinations of 4 base pairs. A set of unique primers was designed for amplification of these tetramers. PCR products were assembled by one step of digestion/ligation reaction. 12 TALE constructs including 4 TALEN pairs targeted to mouse Gt(ROSA)26Sor gene and mouse Mstn gene sequences as well as 4 TALE-TF constructs targeted to mouse Oct4, c-Myc, Klf4 and Sox2 gene promoter sequences were generated by using our method. The construction routines took 3 days and parallel constructions were available. The rate of positive clones during colony PCR verification was 64% on average. Sequencing results suggested that all TALE constructs were performed with high successful rate. This is a rapid and cost-efficient method using the most common enzymes and facilities with a high success rate. PMID:23840477

A simple and efficient method for assembling TALE protein based on plasmid library.

PubMed

Zhang, Zhiqiang; Li, Duo; Xu, Huarong; Xin, Ying; Zhang, Tingting; Ma, Lixia; Wang, Xin; Chen, Zhilong; Zhang, Zhiying

2013-01-01

DNA binding domain of the transcription activator-like effectors (TALEs) from Xanthomonas sp. consists of tandem repeats that can be rearranged according to a simple cipher to target new DNA sequences with high DNA-binding specificity. This technology has been successfully applied in varieties of species for genome engineering. However, assembling long TALE tandem repeats remains a big challenge precluding wide use of this technology. Although several new methodologies for efficiently assembling TALE repeats have been recently reported, all of them require either sophisticated facilities or skilled technicians to carry them out. Here, we described a simple and efficient method for generating customized TALE nucleases (TALENs) and TALE transcription factors (TALE-TFs) based on TALE repeat tetramer library. A tetramer library consisting of 256 tetramers covers all possible combinations of 4 base pairs. A set of unique primers was designed for amplification of these tetramers. PCR products were assembled by one step of digestion/ligation reaction. 12 TALE constructs including 4 TALEN pairs targeted to mouse Gt(ROSA)26Sor gene and mouse Mstn gene sequences as well as 4 TALE-TF constructs targeted to mouse Oct4, c-Myc, Klf4 and Sox2 gene promoter sequences were generated by using our method. The construction routines took 3 days and parallel constructions were available. The rate of positive clones during colony PCR verification was 64% on average. Sequencing results suggested that all TALE constructs were performed with high successful rate. This is a rapid and cost-efficient method using the most common enzymes and facilities with a high success rate.

American Hyperbole: The Tall Tale.

ERIC Educational Resources Information Center

Pavonetti, Linda M.; Combs, Christine M.

1999-01-01

Discusses the historic derivation and the format and characteristics of traditional tall tales, and modern adaptations of these stories. Describes a selection of tall tales for modern young adult readers; notes titles and authors of original tall tales and those with female heroes. Discusses the enduring appeal of traditional and modern tall…

Dissolving Borders and Broadening Perspectives through Latino Traditional Literature.

ERIC Educational Resources Information Center

Smolen, Lynn Atkinson; Ortiz-Castro, Victoria

2000-01-01

Offers a brief historical perspective on Latino folk literature. Discusses 26 recently published books for children and adolescents in both English and Spanish, organized into origin tales, tales based on historical facts, trickster tales, and cumulative tales. Describes activities to use with these books to foster literacy and make powerful…

Brothers Grimm. [Lesson Plan].

ERIC Educational Resources Information Center

Discovery Communications, Inc., Bethesda, MD.

Based on Grimm's fairy tales, this lesson plan presents activities designed to help students understand that fairy tales connect them to earlier generations, help them think about present situations, that magic figures prominently in fairy tales, and that fairy tales can inspire readers to create original works of art. The main activity in the…

Richard Halliburton's Bearded Tales

ERIC Educational Resources Information Center

Morris, Charles E., III

2009-01-01

Fusing the concept of "the beard" with the genre of the tall tale to theorize bearded tales deepens our understanding of closet eloquence, or rhetorical repertories of sexual passing in U.S. history. An examination of adventurer-writer-lecturer Richard Halliburton's sexual provenance and bestselling travel tale, "The Royal Road to Romance" (1925),…

Generation of dTALEs and Libraries of Synthetic TALE-Activated Promoters for Engineering of Gene Regulatory Networks in Plants.

PubMed

Schreiber, Tom; Tissier, Alain

2017-01-01

Transcription factors with programmable DNA-binding specificity constitute valuable tools for the design of orthogonal gene regulatory networks for synthetic biology. Transcription activator-like effectors (TALEs), as natural transcription regulators, were used to design, build, and test libraries of synthetic TALE-activated promoters (STAPs) that show a broad range of expression levels in plants. In this chapter, we present protocols for the construction of artificial TALEs and corresponding STAPs.

TALE proteins search DNA using a rotationally decoupled mechanism.

PubMed

Cuculis, Luke; Abil, Zhanar; Zhao, Huimin; Schroeder, Charles M

2016-10-01

Transcription activator-like effector (TALE) proteins are a class of programmable DNA-binding proteins used extensively for gene editing. Despite recent progress, however, little is known about their sequence search mechanism. Here, we use single-molecule experiments to study TALE search along DNA. Our results show that TALEs utilize a rotationally decoupled mechanism for nonspecific search, despite remaining associated with DNA templates during the search process. Our results suggest that the protein helical structure enables TALEs to adopt a loosely wrapped conformation around DNA templates during nonspecific search, facilitating rapid one-dimensional (1D) diffusion under a range of solution conditions. Furthermore, this model is consistent with a previously reported two-state mechanism for TALE search that allows these proteins to overcome the search speed-stability paradox. Taken together, our results suggest that TALE search is unique among the broad class of sequence-specific DNA-binding proteins and supports efficient 1D search along DNA.

Fairy Tales from Life.

ERIC Educational Resources Information Center

Schulze, Patricia

With the help of the teacher, students will read fairy tales and identify common elements. Choosing common situations and working in small groups, students will draw storyboards of their fairy tale and then write the fairy tale. Project will conclude with class presentations. During ten 50-minute lessons, grade 3-5 students will: listen and read…

Twisters, Tall Tales, & Science Teaching

ERIC Educational Resources Information Center

Wilcox, Dawn Renee; Sterling, Donna R.

2006-01-01

Legends and tall tales have been part of the American culture for ages. Students are probably already familiar with the tales of how Pecos Bill fearlessly tamed a ferocious tornado, or Paul Bunyan effortlessly restrained a great river. Such tales have been passed down from generation to generation to explain humanity, the natural world, and…

A comparative analysis of single cell and droplet-based FACS for improving production phenotypes: Riboflavin overproduction in Yarrowia lipolytica.

PubMed

Wagner, James M; Liu, Leqian; Yuan, Shuo-Fu; Venkataraman, Maya V; Abate, Adam R; Alper, Hal S

2018-04-23

Evolutionary approaches to strain engineering inherently require the identification of suitable selection techniques for the product and phenotype of interest. In this work, we undertake a comparative analysis of two related but functionally distinct methods of high-throughput screening: traditional single cell fluorescence activated cell sorting (single cell FACS) and microdroplet-enabled FACS (droplet FACS) using water/oil/water (w/o/w) emulsions. To do so, we first engineer and evolve the non-conventional yeast Yarrowia lipolytica for high extracellular production of riboflavin (vitamin B2), an innately fluorescent product. Following mutagenesis and adaptive evolution, a direct parity-matched comparison of these two selection strategies was conducted. Both single cell FACS and droplet FACS led to significant increases in total riboflavin titer (32 and 54 fold relative to the parental PO1f strain, respectively). However, single cell FACS favored intracellular riboflavin accumulation (with only 70% of total riboflavin secreted) compared with droplet FACS that favored extracellular product accumulation (with 90% of total riboflavin secreted). We find that for the test case of riboflavin, the extent of secretion and total production were highly correlated. The resulting differences in production modes and levels clearly demonstrate the significant impact that selection approaches can exert on final evolutionary outcomes in strain engineering. Moreover, we note that these results provide a cautionary tale when intracellular read-outs of product concentration (including signals from biosensors) are used as surrogates for total production of potentially secreted products. In this regard, these results demonstrate that extracellular production is best assayed through an encapsulation technique when performing high throughput screening. Copyright © 2018 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Are megacities viable? A cautionary tale from Mexico City.

PubMed

Ezcurra, E; Mazari-hiriart, M

1996-01-01

This article describes the poor environmental and living conditions in Mexico City due to its huge size. Mexico City's size is a challenge to sustainability, and the outcome is unknown. Mexico City and the geographic basin surrounding it included about 18.5 million population in 1995. The basin and surrounding volcanic ranges include nine major environmental zones. Urban growth followed four stages. Different cultures applied different solutions to water supply problems. The basin shifted from self-sufficiency to reliance on 31% of supplies from external watersheds. The water table is declining and canals are polluted. Irrigated agriculture is disappearing. There is an average water deficit of over 800 million cubic meters per year. Mexico City is actually sinking due to groundwater exploitation. There is bacterial contamination of wells due to improper seals. About 75% of the population has access to wastewater treatment and sanitation, but sewage treatment plants operate at under 50% efficiency and treat only about 7% of the total wastewater. Atmospheric pollution from suspended particles has been a problem for decades. Ozone was the most significant air contaminant in 1994. Lead was the most harmful pollutant in 1986. Air pollutants may be the source of submucosal inflammations. Industrial areas are contaminated with suspended particles and sulfur dioxide. High traffic areas have high carbon monoxide levels. Atmospheric pollution has affected the quality of the rainwater. The city survives by importing food, energy, wood, water, building materials, and other products. The development model aims to improve quality of life. The city has been the center of political power since Aztec times, and its preeminent position forces government action. The author concludes that there are limits to urbanization, which the city is approaching rapidly.

Power Imbalances, Food Insecurity, and Children’s Rights in Canada

PubMed Central

Blay-Palmer, Alison

2016-01-01

Increasingly, food is provided through an industrial food system that separates people from the source of their food and results in high rates of food insecurity, particularly for the most vulnerable in society. A lack of food is a symptom of a lack of power in a system that privileges free market principles over social justice and the protection of human rights. In Canada, the high rates of food insecurity among Canadian children is a reflection of their lack of power and the disregard of their human rights, despite the adoption of the United Nations (UN) Convention on the Rights of the Child in 1991 and ratification of the International Covenant on Social, Economic and Cultural Rights in 1976, which established the right to food for all Canadians. Dueling tensions between human rights and market forces underpin this unacceptable state of affairs in Canada. Gaventa’s “power cube” that describes different facets of power – including spaces, levels, and forms – is used to help understand the power imbalances that underlie this injustice. The analysis considers the impact of neoliberal free market principles on the realization of human rights, and the negative impacts this can have on health and well-being for the most vulnerable in society. Canadian case studies from both community organizations provide examples of how power can be shifted to achieve more inclusive, rights-based policy and action. Given increased global pressures toward more open trade markets and national austerity measures that hollow out social supports, Canada provides a cautionary tale for countries in the EU and the US, and for overall approaches to protect the most vulnerable in society. PMID:27563642

Do HCAHPS Doctor Communication Scores Reflect the Communication Skills of the Attending on Record? A Cautionary Tale from a Tertiary-Care Medical Service.

PubMed

Velez, Vicente J; Kaw, Roop; Hu, Bo; Frankel, Richard M; Windover, Amy K; Bokar, Dan; Rish, Julie M; Rothberg, Michael B

2017-06-01

Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores measure patient satisfaction with hospital care. It is not known if these reflect the communication skills of the attending physician on record. The Four Habits Coding Scheme (4HCS) is a validated instrument that measures bedside physician communication skills according to 4 habits, namely: investing in the beginning, eliciting the patient's perspective, demonstrating empathy, and investing in the end. To investigate whether the 4HCS correlates with provider HCAHPS scores. Using a cross-sectional design, consenting hospitalist physicians (n = 28), were observed on inpatient rounds during 3 separate encounters. We compared hospitalists' 4HCS scores with their doctor communication HCAHPS scores to assess the degree to which these correlated with inpatient physician communication skills. We performed sensitivity analysis excluding scores returned by patients cared for by more than 1 hospitalist. A total of 1003 HCAHPS survey responses were available. Pearson correlation between 4HCS and doctor communication scores was not significant, at 0.098 (-0.285, 0.455; P = 0.619). Also, no significant correlations were found between each habit and HCAHPS. When including only scores attributable to 1 hospitalist, Pearson correlation between the empathy habit and the HCAHPS respect score was 0.515 (0.176, 0.745; P = 0.005). Between empathy and overall doctor communication, it was 0.442 (0.082, 0.7; P = 0.019). Attending-of-record HCAHPS scores do not correlate with 4HCS. After excluding patients cared for by more than 1 hospitalist, demonstrating empathy did correlate with the doctor communication and respect HCAHPS scores. Journal of Hospital Medicine 2017;12:421-427. © 2017 Society of Hospital Medicine

A cautionary tale of interpreting O-C diagrams: period instability in a classical RR Lyr Star Z CVn mimicking as a distant companion

NASA Astrophysics Data System (ADS)

Skarka, M.; Liška, J.; Dřevěný, R.; Guggenberger, E.; Sódor, Á.; Barnes, T. G.; Kolenberg, K.

2018-02-01

We present a comprehensive study of Z CVn, an RR Lyrae star that shows long-term cyclic variations of its pulsation period. A possible explanation suggested from the shape of the O-C diagram is the light travel-time effect, which we thoroughly examine. We used original photometric and spectroscopic measurements and investigated the period evolution using available maximum times spanning more than one century. If the binary hypothesis is valid, Z CVn orbits around a black hole with minimal mass of 56.5 M_{⊙} on a very wide (Porbit = 78.3 yr) and eccentric orbit (e = 0.63). We discuss the probability of the formation of a black hole-RR Lyrae pair, and, although we found it possible, there is no observational evidence of the black hole in the direction to Z CVn. However, the main objection against the binary hypothesis is the comparison of the systemic radial velocity curve model and spectroscopic observations that clearly show that Z CVn cannot be bound in such a binary. Therefore, the variations of pulsation period are likely intrinsic to the star. This finding represents a discovery/confirmation of a new type of cyclic period changes in RR Lyrae stars. By the analysis of our photometric data, we found that the Blazhko modulation with period of 22.931 d is strongly dominant in amplitude. The strength of the phase modulation varies and is currently almost undetectable. We also estimated photometric physical parameters of Z CVn and investigated their variations during the Blazhko cycle using the inverse Baade-Wesselink method.

Mixed reality ultrasound guidance system: a case study in system development and a cautionary tale.

PubMed

Ameri, Golafsoun; Baxter, John S H; Bainbridge, Daniel; Peters, Terry M; Chen, Elvis C S

2018-04-01

Real-time ultrasound has become a crucial aspect of several image-guided interventions. One of the main constraints of such an approach is the difficulty in interpretability of the limited field of view of the image, a problem that has recently been addressed using mixed reality, such as augmented reality and augmented virtuality. The growing popularity and maturity of mixed reality has led to a series of informal guidelines to direct development of new systems and to facilitate regulatory approval. However, the goals of mixed reality image guidance systems and the guidelines for their development have not been thoroughly discussed. The purpose of this paper is to identify and critically examine development guidelines in the context of a mixed reality ultrasound guidance system through a case study. A mixed reality ultrasound guidance system tailored to central line insertions was developed in close collaboration with an expert user. This system outperformed ultrasound-only guidance in a novice user study and has obtained clearance for clinical use in humans. A phantom study with 25 experienced physicians was carried out to compare the performance of the mixed reality ultrasound system against conventional ultrasound-only guidance. Despite the previous promising results, there was no statistically significant difference between the two systems. Guidelines for developing mixed reality image guidance systems cannot be applied indiscriminately. Each design decision, no matter how well justified, should be the subject of scientific and technical investigation. Iterative and small-scale evaluation can readily unearth issues and previously unknown or implicit system requirements. We recommend a wary eye in development of mixed reality ultrasound image guidance systems emphasizing small-scale iterative evaluation alongside system development. Ultimately, we recommend that the image-guided intervention community furthers and deepens this discussion into best practices in developing image-guided interventions.

Management of colon wounds in the setting of damage control laparotomy: a cautionary tale.

PubMed

Weinberg, Jordan A; Griffin, Russell L; Vandromme, Marianne J; Melton, Sherry M; George, Richard L; Reiff, Donald A; Kerby, Jeffrey D; Rue, Loring W

2009-11-01

Although colon wounds are commonly treated in the setting of damage control laparotomy (DCL), a paucity of data exist to guide management. The purpose of this study was to evaluate our experience with the management of colonic wounds in the context of DCL, using colonic wound outcomes after routine, single laparotomy (SL) as a benchmark. Consecutive patients during a 7-year period with full-thickness or devitalizing colon injury were identified. Early deaths (<48 hour) were excluded. Colon-related complications (abscess, suture or staple leak, and stomal ischemia) were compared between those managed in the setting of DCL versus those managed by SL, both overall and as stratified by procedure (primary repair, resection and anastomosis, and resection and colostomy). One hundred fifty-seven patients met study criteria: 101 had undergone SL and 56 had undergone DCL. Comparison of DCL patients with SL patients was notable for a significant difference in colon-related complications (30% vs. 12%, p < 0.005) and suture/staple leak in particular (12% vs. 3%, p < 0.05). Stratification by procedure revealed a significant difference in colon-related complications among those that underwent resection and anastomosis (DCL: 39% vs. SL: 18%, p < 0.05), whereas no differences were observed in those who underwent primary repair or resection and colostomy. Management of colonic wounds in the setting of DCL is associated with a relatively high incidence of complications. The excessive incidence of leak overall and morbidity particular to resection and anastomosis, however, give us pause. Although stoma construction is not without its own complications in the setting of DCL, it may be the safer alternative.

Stratified randomization controls better for batch effects in 450K methylation analysis: a cautionary tale.

PubMed

Buhule, Olive D; Minster, Ryan L; Hawley, Nicola L; Medvedovic, Mario; Sun, Guangyun; Viali, Satupaitea; Deka, Ranjan; McGarvey, Stephen T; Weeks, Daniel E

2014-01-01

Batch effects in DNA methylation microarray experiments can lead to spurious results if not properly handled during the plating of samples. Two pilot studies examining the association of DNA methylation patterns across the genome with obesity in Samoan men were investigated for chip- and row-specific batch effects. For each study, the DNA of 46 obese men and 46 lean men were assayed using Illumina's Infinium HumanMethylation450 BeadChip. In the first study (Sample One), samples from obese and lean subjects were examined on separate chips. In the second study (Sample Two), the samples were balanced on the chips by lean/obese status, age group, and census region. We used methylumi, watermelon, and limma R packages, as well as ComBat, to analyze the data. Principal component analysis and linear regression were, respectively, employed to identify the top principal components and to test for their association with the batches and lean/obese status. To identify differentially methylated positions (DMPs) between obese and lean males at each locus, we used a moderated t-test. Chip effects were effectively removed from Sample Two but not Sample One. In addition, dramatic differences were observed between the two sets of DMP results. After "removing" batch effects with ComBat, Sample One had 94,191 probes differentially methylated at a q-value threshold of 0.05 while Sample Two had zero differentially methylated probes. The disparate results from Sample One and Sample Two likely arise due to the confounding of lean/obese status with chip and row batch effects. Even the best possible statistical adjustments for batch effects may not completely remove them. Proper study design is vital for guarding against spurious findings due to such effects.

Stratified randomization controls better for batch effects in 450K methylation analysis: a cautionary tale

PubMed Central

Buhule, Olive D.; Minster, Ryan L.; Hawley, Nicola L.; Medvedovic, Mario; Sun, Guangyun; Viali, Satupaitea; Deka, Ranjan; McGarvey, Stephen T.; Weeks, Daniel E.

2014-01-01

Background: Batch effects in DNA methylation microarray experiments can lead to spurious results if not properly handled during the plating of samples. Methods: Two pilot studies examining the association of DNA methylation patterns across the genome with obesity in Samoan men were investigated for chip- and row-specific batch effects. For each study, the DNA of 46 obese men and 46 lean men were assayed using Illumina's Infinium HumanMethylation450 BeadChip. In the first study (Sample One), samples from obese and lean subjects were examined on separate chips. In the second study (Sample Two), the samples were balanced on the chips by lean/obese status, age group, and census region. We used methylumi, watermelon, and limma R packages, as well as ComBat, to analyze the data. Principal component analysis and linear regression were, respectively, employed to identify the top principal components and to test for their association with the batches and lean/obese status. To identify differentially methylated positions (DMPs) between obese and lean males at each locus, we used a moderated t-test. Results: Chip effects were effectively removed from Sample Two but not Sample One. In addition, dramatic differences were observed between the two sets of DMP results. After “removing” batch effects with ComBat, Sample One had 94,191 probes differentially methylated at a q-value threshold of 0.05 while Sample Two had zero differentially methylated probes. The disparate results from Sample One and Sample Two likely arise due to the confounding of lean/obese status with chip and row batch effects. Conclusion: Even the best possible statistical adjustments for batch effects may not completely remove them. Proper study design is vital for guarding against spurious findings due to such effects. PMID:25352862

Methodological constraints in interpreting serum paraoxonase-1 activity measurements: an example from a study in HIV-infected patients.

PubMed

Parra, Sandra; Marsillach, Judit; Aragonès, Gerard; Rull, Anna; Beltrán-Debón, Raúl; Alonso-Villaverde, Carlos; Joven, Jorge; Camps, Jordi

2010-03-25

Paraoxonase-1 (PON1) is an antioxidant enzyme that attenuates the production of the monocyte chemoattractant protein-1 (MCP-1) in vitro. Although oxidation and inflammation are closely related processes, the association between PON1 and MCP-1 has not been completely characterised due, probably, to that the current use of synthetic substrates for PON1 measurement limits the interpretation of the data. In the present study, we explored the relationships between the circulating levels of PON1 and MCP-1 in human immunodeficiency virus-infected patients in relation to the multifunctional capabilities of PON1. We measured selected variables in 227 patients and in a control group of 409 participants. Serum PON1 esterase and lactonase activities were measured as the rates of hydrolysis of paraoxon and of 5-(thiobutyl)-butyrolactone, respectively. Oxidised LDL and MCP-1 concentrations were determined by enzyme-linked immunosorbent assay. High-density lipoproteins cholesterol, apolipoprotein A-I, and C-reactive protein concentrations were measured by standard automated methods. There were significant relationships between PON1 activity and several indices of oxidation and inflammation in control subjects and in infected patients. However, these relationships varied not only with disease status but also on the type of substrate used for PON1 measurement. The present study is a cautionary tale highlighting that results of clinical studies on PON1 may vary depending on the methods used as well as the disease studied. Until more specific methods using physiologically-akin substrates are developed for PON1 measurement, we suggest the simultaneous employment of at least two different substrates in order to improve the reliability of the results obtained.

Who is bearing the financial burden of non-communicable diseases in Mongolia?

PubMed Central

Dugee, Otgontuya; Palam, Enkhtuya; Dorjsuren, Bayarsaikhan; Mahal, Ajay

2018-01-01

Background Non-communicable diseases (NCDs) pose a formidable health and development challenge for low- and middle-income countries (LMICs). However, translating this challenge into resource allocation is seriously constrained by a lack of country specific evidence on NCD financing and its distributional implications. This study estimated expenditures associated with NCDs in Mongolia and their distributions across socioeconomic groups, focusing especially on private out-of-pocket (OOP) spending on the major NCDs. Methods Secondary data analysis of multiple data sources on NCD related health service use and expenditures including detailed administrative data, World Health Organization STEPwise approach to Surveillance (STEPs) survey for Mongolia, and household surveys. Sample-weighted estimates of OOP expenditures for NCDs were constructed using STEPs data. OOP payments per discharge and per outpatient visit were estimated by condition and type of service provider, and survey data on utilization, after adjusting for utilization in administrative records. Results NCDs in Mongolia accounted for more than one-third of total health expenditures in 2013. A significant fraction of this expenditure was borne by households in the form of OOP spending. CVD-related health spending is the major driver of NCD-spending in Mongolia, accounting for about 24.2% of total health expenditure. OOP health payments, largely driven by outpatient diagnostics and drugs, were incurred disproportionately by the better-off, seeking more specialist services and better quality private care. Conclusion A high share of OOP spending for NCDs in Mongolia, which ostensibly enjoys universal health coverage, provides a cautionary tale for LMICs in a similar situation. Improvement in the quality of services at the primary care level and rural health care facilities, where the poor mainly attend, is desirable together with an effective exemption policy for user fees at higher level hospitals. PMID:29564086

Body growth and reproduction of individuals of the sciaenid fish Stellifer rastrifer in a shallow tropical bight: A cautionary tale for assumptions regarding population parameters

NASA Astrophysics Data System (ADS)

Pombo, Maíra; Denadai, Márcia Regina; Turra, Alexander

2013-05-01

Knowledge of population parameters and the ability to predict their responses to environmental changes are useful tools to aid in the appropriate management and conservation of natural resources. Samples of the sciaenid fish Stellifer rastrifer were taken from August 2003 through October 2004 in shallow areas of Caraguatatuba Bight, southeastern Brazil. The results showed a consistent presence of length-frequency classes throughout the year and low values of the gonadosomatic index of this species, indicating that the area is not used for spawning or residence of adults, but rather shelters individuals in late stages of development. The results may serve as a caveat for assessments of transitional areas such as the present one, the nursery function of which is neglected compared to estuaries and mangroves. The danger of mismanaging these areas by not considering their peculiarities is emphasized by using these data as a study case for the development of some broadly used population-parameter analyses. The individuals' body growth parameters from the von Bertalanffy model were estimated based on the most common approaches, and the best values obtained from traditional quantification methods of selection were very prone to bias. The low gonadosomatic index (GSI) estimated during the period was an important factor in stimulating us to select more reliable parameters of body growth (L∞ = 20.9, K = 0.37 and Z = 2.81), which were estimated based on assuming the existence of spatial segregation by size. The data obtained suggest that the estimated mortality rate included a high rate of migration of older individuals to deeper areas, where we assume that they completed their development.

A cautionary tale: the non-causal association between type 2 diabetes risk SNP, rs7756992, and levels of non-coding RNA, CDKAL1-v1.

PubMed

Locke, Jonathan M; Wei, Fan-Yan; Tomizawa, Kazuhito; Weedon, Michael N; Harries, Lorna W

2015-04-01

Intronic single nucleotide polymorphisms (SNPs) in the CDKAL1 gene are associated with risk of developing type 2 diabetes. A strong correlation between risk alleles and lower levels of the non-coding RNA, CDKAL1-v1, has recently been reported in whole blood extracted from Japanese individuals. We sought to replicate this association in two independent cohorts: one using whole blood from white UK-resident individuals, and one using a collection of human pancreatic islets, a more relevant tissue type to study with respect to the aetiology of diabetes. Levels of CDKAL1-v1 were measured by real-time PCR using RNA extracted from human whole blood (n = 70) and human pancreatic islets (n = 48). Expression with respect to genotype was then determined. In a simple linear regression model, expression of CDKAL1-v1 was associated with the lead type 2 diabetes-associated SNP, rs7756992, in whole blood and islets. However, these associations were abolished or substantially reduced in multiple regression models taking into account rs9366357 genotype: a moderately linked SNP explaining a much larger amount of the variation in CDKAL1-v1 levels, but not strongly associated with risk of type 2 diabetes. Contrary to previous findings, we provide evidence against a role for dysregulated expression of CDKAL1-v1 in mediating the association between intronic SNPs in CDKAL1 and susceptibility to type 2 diabetes. The results of this study illustrate how caution should be exercised when inferring causality from an association between disease-risk genotype and non-coding RNA expression.

Season and preterm birth in Norway: A cautionary tale

PubMed Central

Weinberg, Clarice R; Shi, Min; DeRoo, Lisa A; Basso, Olga; Skjærven, Rolv

2015-01-01

Background: Preterm birth is a common, costly and dangerous pregnancy complication. Seasonality of risk would suggest modifiable causes. Methods: We examine seasonal effects on preterm birth, using data from the Medical Birth Registry of Norway (2 321 652 births), and show that results based on births are misleading and a fetuses-at-risk approach is essential. In our harmonic-regression Cox proportional hazards model we consider fetal risk of birth between 22 and 37 completed weeks of gestation. We examine effects of both day of year of conception (for early effects) and day of ongoing gestation (for seasonal effects on labour onset) as modifiers of gestational-age-based risk. Results: Naïve analysis of preterm rates across days of birth shows compelling evidence for seasonality (P < 10−152). However, the reconstructed numbers of conceptions also vary with season (P < 10−307), confounding results by inducing seasonal variation in the age distribution of the fetal population at risk. When we instead properly treat fetuses as the individuals at risk, restrict analysis to pregnancies with relatively accurate ultrasound-based assessment of gestational age (available since 1998) and adjust for socio-demographic factors and maternal smoking, we find modest effects of both time of year of conception and time of year at risk, with peaks for early preterm near early January and early July. Conclusions: Analyses of seasonal effects on preterm birth are demonstrably vulnerable to confounding by seasonality of conception, measurement error in conception dating, and socio-demographic factors. The seasonal variation based on fetuses reveals two peaks for early preterm, coinciding with New Year’s Day and the early July beginning of Norway’s summer break, and may simply reflect a holiday-related pattern of unintended conception. PMID:26045507

"They got their program, and I got mine": a cautionary tale concerning the ethical implications of using respondent-driven sampling to study injection drug users.

PubMed

Scott, Greg

2008-02-01

This article examines the ethical implications of using respondent-driven sampling (RDS) to conduct HIV behaviour surveillance among injection drug users (IDUs) in Chicago. Ethnographic inquiry illustrates how the design and implementation of RDS invites if not promotes manifold violations of federal guidelines governing human research subject protections. Post hoc structured interviews with approximately 13% (n=70) of the behaviour surveillance sample (N=529) focused on how RDS's "dual incentive" structure affected participants' social, economic, and cultural milieu. Triangulated methods include interviews with owners of 20 "shooting galleries", unofficial and illegal locales where IDUs congregate and 400 h of traditional ethnographic observation of individual IDUs and IDU networks. "Consensus analysis" allows identification of key cultural domains that define the RDS coupon market. The study reveals the power of RDS to foment a stratified market of research participation that reinforces pre-existing economic and social inequalities among IDUs. Participants co-opted RDS to develop various "underground" revenue-generating modalities that produced differential risks and benefits among participants. Deleterious outcomes include false advertising regarding the study's risks and benefits, exploitation of relative economic deprivation, generation of sero-discordant social networks, and interpersonal and organised conflict, coercion, and violence. Although RDS may involve serious ethical violations it remains the best available means for accruing a representative sample of hidden populations. It is critical, however, to supplement RDS with research into (1) the subjects' cultural, social, economic, and political contexts, (2) the potential human subjects violations that participants experience, and (3) how these two issues might affect data integrity and interpretation.

Importance of elastic finite-size effects: Neutral defects in ionic compounds

DOE PAGES

Burr, P. A.; Cooper, M. W. D.

2017-09-15

Small system sizes are a well known source of error in DFT calculations, yet computational constraints frequently dictate the use of small supercells, often as small as 96 atoms in oxides and compound semiconductors. In ionic compounds, electrostatic finite size effects have been well characterised, but self-interaction of charge neutral defects is often discounted or assumed to follow an asymptotic behaviour and thus easily corrected with linear elastic theory. Here we show that elastic effect are also important in the description of defects in ionic compounds and can lead to qualitatively incorrect conclusions if inadequatly small supercells are used; moreover,more » the spurious self-interaction does not follow the behaviour predicted by linear elastic theory. Considering the exemplar cases of metal oxides with fluorite structure, we show that numerous previous studies, employing 96-atom supercells, misidentify the ground state structure of (charge neutral) Schottky defects. We show that the error is eliminated by employing larger cells (324, 768 and 1500 atoms), and careful analysis determines that elastic effects, not electrostatic, are responsible. The spurious self-interaction was also observed in non-oxide ionic compounds and irrespective of the computational method used, thereby resolving long standing discrepancies between DFT and force-field methods, previously attributed to the level of theory. The surprising magnitude of the elastic effects are a cautionary tale for defect calculations in ionic materials, particularly when employing computationally expensive methods (e.g. hybrid functionals) or when modelling large defect clusters. We propose two computationally practicable methods to test the magnitude of the elastic self-interaction in any ionic system. In commonly studies oxides, where electrostatic effects would be expected to be dominant, it is the elastic effects that dictate the need for larger supercells | greater than 96 atoms.« less

Opening the file drawer: Unexpected insights from a chytrid infection experiment.

PubMed

Byrne, Allison Q; Poorten, Thomas J; Voyles, Jamie; Willis, Craig K R; Rosenblum, Erica Bree

2018-01-01

Infection experiments are critical for understanding wildlife disease dynamics. Although infection experiments are typically designed to reduce complexity, disease outcomes still result from complex interactions between host, pathogen, and environmental factors. Cryptic variation across factors can lead to decreased repeatability of infection experiments within and between research groups and hinder research progress. Furthermore, studies with unexpected results are often relegated to the "file drawer" and potential insights gained from these experimental outcomes are lost. Here, we report unexpected results from an infection experiment studying the response of two differentially-susceptible but related frogs (American Bullfrog Rana catesbeiana and the Mountain yellow-legged frog Rana muscosa) to the amphibian-killing chytrid fungus (Batrachochytrium dendrobatidis, Bd). Despite well-documented differences in susceptibility between species, we found no evidence for antibody-mediated immune response and no Bd-related mortality in either species. Additionally, during the study, the sham-inoculated R. catesbeiana control group became unexpectedly Bd-positive. We used a custom genotyping assay to demonstrate that the aberrantly-infected R. catesbeiana carried a Bd genotype distinct from the inoculation genotype. Thus R. catesbeiana individuals were acquired with low-intensity infections that could not be detected with qPCR. In the Bd-inoculated R. catesbeiana treatment group, the inoculated genotype appeared to out-compete the cryptic infection. Thus, our results provide insight into Bd coinfection dynamics, a phenomenon that is increasingly relevant as different pathogen strains are moved around the globe. Our experiment highlights how unexpected experimental outcomes can serve as both cautionary tales and opportunities to explore unanswered research questions. We use our results as a case study to highlight common sources of anomalous results for infection experiments. We argue that understanding these factors will aid researchers in the design, execution, and interpretation of experiments to understand wildlife disease processes.

Importance of elastic finite-size effects: Neutral defects in ionic compounds

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

Burr, P. A.; Cooper, M. W. D.

Small system sizes are a well known source of error in DFT calculations, yet computational constraints frequently dictate the use of small supercells, often as small as 96 atoms in oxides and compound semiconductors. In ionic compounds, electrostatic finite size effects have been well characterised, but self-interaction of charge neutral defects is often discounted or assumed to follow an asymptotic behaviour and thus easily corrected with linear elastic theory. Here we show that elastic effect are also important in the description of defects in ionic compounds and can lead to qualitatively incorrect conclusions if inadequatly small supercells are used; moreover,more » the spurious self-interaction does not follow the behaviour predicted by linear elastic theory. Considering the exemplar cases of metal oxides with fluorite structure, we show that numerous previous studies, employing 96-atom supercells, misidentify the ground state structure of (charge neutral) Schottky defects. We show that the error is eliminated by employing larger cells (324, 768 and 1500 atoms), and careful analysis determines that elastic effects, not electrostatic, are responsible. The spurious self-interaction was also observed in non-oxide ionic compounds and irrespective of the computational method used, thereby resolving long standing discrepancies between DFT and force-field methods, previously attributed to the level of theory. The surprising magnitude of the elastic effects are a cautionary tale for defect calculations in ionic materials, particularly when employing computationally expensive methods (e.g. hybrid functionals) or when modelling large defect clusters. We propose two computationally practicable methods to test the magnitude of the elastic self-interaction in any ionic system. In commonly studies oxides, where electrostatic effects would be expected to be dominant, it is the elastic effects that dictate the need for larger supercells | greater than 96 atoms.« less

Importance of elastic finite-size effects: Neutral defects in ionic compounds

NASA Astrophysics Data System (ADS)

Burr, P. A.; Cooper, M. W. D.

2017-09-01

Small system sizes are a well-known source of error in density functional theory (DFT) calculations, yet computational constraints frequently dictate the use of small supercells, often as small as 96 atoms in oxides and compound semiconductors. In ionic compounds, electrostatic finite-size effects have been well characterized, but self-interaction of charge-neutral defects is often discounted or assumed to follow an asymptotic behavior and thus easily corrected with linear elastic theory. Here we show that elastic effects are also important in the description of defects in ionic compounds and can lead to qualitatively incorrect conclusions if inadequately small supercells are used; moreover, the spurious self-interaction does not follow the behavior predicted by linear elastic theory. Considering the exemplar cases of metal oxides with fluorite structure, we show that numerous previous studies, employing 96-atom supercells, misidentify the ground-state structure of (charge-neutral) Schottky defects. We show that the error is eliminated by employing larger cells (324, 768, and 1500 atoms), and careful analysis determines that elastic, not electrostatic, effects are responsible. The spurious self-interaction was also observed in nonoxide ionic compounds irrespective of the computational method used, thereby resolving long-standing discrepancies between DFT and force-field methods, previously attributed to the level of theory. The surprising magnitude of the elastic effects is a cautionary tale for defect calculations in ionic materials, particularly when employing computationally expensive methods (e.g., hybrid functionals) or when modeling large defect clusters. We propose two computationally practicable methods to test the magnitude of the elastic self-interaction in any ionic system. In commonly studied oxides, where electrostatic effects would be expected to be dominant, it is the elastic effects that dictate the need for larger supercells: greater than 96 atoms.

Ugiuvangmiut Quliapyuit = King Island Tales. Eskimo History and Legends from Bering Strait.

ERIC Educational Resources Information Center

Kaplan, Lawrence D., Ed.

The collection of native tales from King Island, Alaska, contains tales told originally in Inupiaq Eskimo by seven native elders. Introductory sections provide background information on the storytellers, King Island Village and its people, traditional life there, and the language of the King Islanders. The 25 tales are divided into groups:…

Writing and Retelling Multiple Ethnographic Tales of a Soup Kitchen for the Homeless.

ERIC Educational Resources Information Center

Miller, Dana L.; Creswell, John W.; Olander, Lisa

An ethnographic study narrated three tales about a soup kitchen for the homeless and the near-homeless. To provide a cultural, ethnographic analysis, and share fieldwork experiences the study began with realist and confessional tales. These two tales emerged from the initial writing and presenting of the soup kitchen ethnography to qualitative…

Comprehensive Interrogation of Natural TALE DNA Binding Modules and Transcriptional Repressor Domains

PubMed Central

Cong, Le; Zhou, Ruhong; Kuo, Yu-chi; Cunniff, Margaret; Zhang, Feng

2012-01-01

Transcription activator-like effectors (TALE) are sequence-specific DNA binding proteins that harbor modular, repetitive DNA binding domains. TALEs have enabled the creation of customizable designer transcriptional factors and sequence-specific nucleases for genome engineering. Here we report two improvements of the TALE toolbox for achieving efficient activation and repression of endogenous gene expression in mammalian cells. We show that the naturally occurring repeat variable diresidue (RVD) Asn-His (NH) has high biological activity and specificity for guanine, a highly prevalent base in mammalian genomes. We also report an effective TALE transcriptional repressor architecture for targeted inhibition of transcription in mammalian cells. These findings will improve the precision and effectiveness of genome engineering that can be achieved using TALEs. PMID:22828628

Molecular Dynamics Simulations of DNA-Free and DNA-Bound TAL Effectors

PubMed Central

Wan, Hua; Hu, Jian-ping; Li, Kang-shun; Tian, Xu-hong; Chang, Shan

2013-01-01

TAL (transcriptional activator-like) effectors (TALEs) are DNA-binding proteins, containing a modular central domain that recognizes specific DNA sequences. Recently, the crystallographic studies of TALEs revealed the structure of DNA-recognition domain. In this article, molecular dynamics (MD) simulations are employed to study two crystal structures of an 11.5-repeat TALE, in the presence and absence of DNA, respectively. The simulated results indicate that the specific binding of RVDs (repeat-variable diresidues) with DNA leads to the markedly reduced fluctuations of tandem repeats, especially at the two ends. In the DNA-bound TALE system, the base-specific interaction is formed mainly by the residue at position 13 within a TAL repeat. Tandem repeats with weak RVDs are unfavorable for the TALE-DNA binding. These observations are consistent with experimental studies. By using principal component analysis (PCA), the dominant motions are open-close movements between the two ends of the superhelical structure in both DNA-free and DNA-bound TALE systems. The open-close movements are found to be critical for the recognition and binding of TALE-DNA based on the analysis of free energy landscape (FEL). The conformational analysis of DNA indicates that the 5′ end of DNA target sequence has more remarkable structural deformability than the other sites. Meanwhile, the conformational change of DNA is likely associated with the specific interaction of TALE-DNA. We further suggest that the arrangement of N-terminal repeats with strong RVDs may help in the design of efficient TALEs. This study provides some new insights into the understanding of the TALE-DNA recognition mechanism. PMID:24130757

Evolution of Transcription Activator-Like Effectors in Xanthomonas oryzae

PubMed Central

Erkes, Annett; Reschke, Maik; Boch, Jens

2017-01-01

Abstract Transcription activator-like effectors (TALEs) are secreted by plant–pathogenic Xanthomonas bacteria into plant cells where they act as transcriptional activators and, hence, are major drivers in reprogramming the plant for the benefit of the pathogen. TALEs possess a highly repetitive DNA-binding domain of typically 34 amino acid (AA) tandem repeats, where AA 12 and 13, termed repeat variable di-residue (RVD), determine target specificity. Different Xanthomonas strains possess different repertoires of TALEs. Here, we study the evolution of TALEs from the level of RVDs determining target specificity down to the level of DNA sequence with focus on rice-pathogenic Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc) strains. We observe that codon pairs coding for individual RVDs are conserved to a similar degree as the flanking repeat sequence. We find strong indications that TALEs may evolve 1) by base substitutions in codon pairs coding for RVDs, 2) by recombination of N-terminal or C-terminal regions of existing TALEs, or 3) by deletion of individual TALE repeats, and we propose possible mechanisms. We find indications that the reassortment of TALE genes in clusters is mediated by an integron-like mechanism in Xoc. We finally study the effect of the presence/absence and evolutionary modifications of TALEs on transcriptional activation of putative target genes in rice, and find that even single RVD swaps may lead to considerable differences in activation. This correlation allowed a refined prediction of TALE targets, which is the crucial step to decipher their virulence activity. PMID:28637323

Non-RVD mutations that enhance the dynamics of the TAL repeat array along the superhelical axis improve TALEN genome editing efficacy

PubMed Central

Tochio, Naoya; Umehara, Kohei; Uewaki, Jun-ichi; Flechsig, Holger; Kondo, Masaharu; Dewa, Takehisa; Sakuma, Tetsushi; Yamamoto, Takashi; Saitoh, Takashi; Togashi, Yuichi; Tate, Shin-ichi

2016-01-01

Transcription activator-like effector (TALE) nuclease (TALEN) is widely used as a tool in genome editing. The DNA binding part of TALEN consists of a tandem array of TAL-repeats that form a right-handed superhelix. Each TAL-repeat recognises a specific base by the repeat variable diresidue (RVD) at positions 12 and 13. TALEN comprising the TAL-repeats with periodic mutations to residues at positions 4 and 32 (non-RVD sites) in each repeat (VT-TALE) exhibits increased efficacy in genome editing compared with a counterpart without the mutations (CT-TALE). The molecular basis for the elevated efficacy is unknown. In this report, comparison of the physicochemical properties between CT- and VT-TALEs revealed that VT-TALE has a larger amplitude motion along the superhelical axis (superhelical motion) compared with CT-TALE. The greater superhelical motion in VT-TALE enabled more TAL-repeats to engage in the target sequence recognition compared with CT-TALE. The extended sequence recognition by the TAL-repeats improves site specificity with limiting the spatial distribution of FokI domains to facilitate their dimerization at the desired site. Molecular dynamics simulations revealed that the non-RVD mutations alter inter-repeat hydrogen bonding to amplify the superhelical motion of VT-TALE. The TALEN activity is associated with the inter-repeat hydrogen bonding among the TAL repeats. PMID:27883072

Through Fairy-Tales to Math in the Lessons

ERIC Educational Resources Information Center

Andersone, Rudite

2009-01-01

Every person in his lifetime has many times experienced the miraculous impact of the fairy-tale on his imagination, mind and feelings. But we seldom reflect upon the content not only in the ethical aspect of fairy-tales but also as a source of different kinds of knowledge, among them the knowledge of mathematics. The use of fairy-tales in lessons…

Introducing Children to Folk Tales. Bill Harp Professional Teachers Library.

ERIC Educational Resources Information Center

Weir, Beth

This book provides K-8 teachers with an introductory resource on folk tales. The book acknowledges that teachers are often very interested in folk tales but lack the time to research them. Each chapter contains some background information on a story type or a character. The book's six chapters are as follows: (1) "The Folk Tale Tradition"; (2)…

Exploring Online Purchasing.

ERIC Educational Resources Information Center

Fickes, Michael

2001-01-01

Examines the setup of American University's electronic procurement system and explains how it works and the benefits it brings to the school. Cautionary advice on setting up an online purchasing system is also offered. (GR)

Evaluation of Current Consensus Statement Recommendations for Accelerated Partial Breast Irradiation: A Pooled Analysis of William Beaumont Hospital and American Society of Breast Surgeon MammoSite Registry Trial Data

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

Wilkinson, J. Ben; Beitsch, Peter D.; Shah, Chirag

Purpose: To determine whether the American Society for Radiation Oncology (ASTRO) Consensus Statement (CS) recommendations for accelerated partial breast irradiation (APBI) are associated with significantly different outcomes in a pooled analysis from William Beaumont Hospital (WBH) and the American Society of Breast Surgeons (ASBrS) MammoSite® Registry Trial. Methods and Materials: APBI was used to treat 2127 cases of early-stage breast cancer (WBH, n=678; ASBrS, n=1449). Three forms of APBI were used at WBH (interstitial, n=221; balloon-based, n=255; or 3-dimensional conformal radiation therapy, n=206), whereas all Registry Trial patients received balloon-based brachytherapy. Patients were divided according to the ASTRO CS intomore » suitable (n=661, 36.5%), cautionary (n=850, 46.9%), and unsuitable (n=302, 16.7%) categories. Tumor characteristics and clinical outcomes were analyzed according to CS group. Results: The median age was 65 years (range, 32-94 years), and the median tumor size was 10.0 mm (range, 0-45 mm). The median follow-up time was 60.6 months. The WBH cohort had more node-positive disease (6.9% vs 2.6%, P<.01) and cautionary patients (49.5% vs 41.8%, P=.06). The 5-year actuarial ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), and distant metastasis (DM) for the whole cohort were 2.8%, 0.6%, 1.6%. The rate of IBTR was not statistically higher between suitable (2.5%), cautionary (3.3%), or unsuitable (4.6%) patients (P=.20). The nonsignificant increase in IBTR for the cautionary and unsuitable categories was due to increased elsewhere failures and new primaries (P=.04), not tumor bed recurrence (P=.93). Conclusions: Excellent outcomes after breast-conserving surgery and APBI were seen in our pooled analysis. The current ASTRO CS guidelines did not adequately differentiate patients at an increased risk of IBTR or tumor bed failure in this large patient cohort.« less

Morality's ugly implications in Oscar Wilde's fairy tales.

PubMed

Jones, Justin T

2011-01-01

In Oscar Wilde's two volumes of fairy tales, "The Happy Prince" and Other Tales (1888) and A House of Pomegranates (1891), many central characters meet with premature death or physical disfigurement after learning a bourgeois moral lesson. In an attempt to explain this unconventional phenomenon in the fairy tale tradition, this essay examines Wilde's stories through the lens of his aesthetic ideology and demonstrates how the superficial morality of the Victorian bourgeoisie corrodes each tale's aesthetic integrity, causing the characters to either deny morality outright, assume the guise of Christian philanthropy, or die as the result of their moral reformation.

Tales of Wisdom in Folly. A Course in Controlled Composition. Program and Training Journal Reprint Series, No. 13.

ERIC Educational Resources Information Center

Kayeum, Joan

This booklet is a collection of Mullah Nasruddin tales that are commonly enjoyed in Afghanistan. These tales have been adapted to form a course in controlled composition for students studying English as a foreign language. After reading each tale the student is asked to carry out certain tasks. In addition to the simplest task, copying the passage…

The Fantastic Tale for Children: A Genre Study from the Viewpoints of Literary and Educational Research.

ERIC Educational Resources Information Center

Klingberg, Gote

The literary genre explored in this study is The Fantastic Tale for Children, which combines magic and reality. Two examples of the "pure" fantastic tale are "The Return of the Twelves" by Pauline Clarke and "Tom's Midnight Garden" by Philippa Pearce. The motifs of the fantastic tale are methods which connect the world of the principal characters…

Tell Me a Fairy Tale: A Parent's Guide to Telling Magical and Mythical Stories.

ERIC Educational Resources Information Center

Adler, Bill, Jr.

Designed to help parents tell and retell their children's favorite fairy tales and stories, this collection condenses dozens of plots and lists characters, so that the parent can make a tale as long or as short as a sleepy child needs, personalize the story, and convey the true wonder of the originals through the spoken voice. The 64 tales in the…

Meteor Beliefs Project: Meteoric imagery in SF, Part II - H. P. Lovecraft's The Colour Out Of Space

NASA Astrophysics Data System (ADS)

McBeath, Alastair; Gheorghe, Andrei Dorian

2005-12-01

A brief biography of American horror-fiction writer H. P. Lovecraft (1890-1937) precedes details from his story `The Colour Out Of Space', concerning a deadly life-form brought to Earth in a meteorite. This allows a comparison with details from the 1965 film derived from this tale, `Die, Monster, Die!', featuring the great horror actor Boris Karloff in one of his last, best roles.

Designer TAL effectors induce disease susceptibility and resistance to Xanthomonas oryzae pv. oryzae in rice.

PubMed

Li, Ting; Huang, Sheng; Zhou, Junhui; Yang, Bing

2013-05-01

TAL (transcription activator-like) effectors from Xanthomonas bacteria activate the cognate host genes, leading to disease susceptibility or resistance dependent on the genetic context of host target genes. The modular nature and DNA recognition code of TAL effectors enable custom-engineering of designer TAL effectors (dTALE) for gene activation. However, the feasibility of dTALEs as transcription activators for gene functional analysis has not been demonstrated. Here, we report the use of dTALEs, as expressed and delivered by the pathogenic Xanthomonas oryzae pv. oryzae (Xoo), in revealing the new function of two previously identified disease-related genes and the potential of one developmental gene for disease susceptibility in rice/Xoo interactions. The dTALE gene dTALE-xa27, designed to target the susceptible allele of the resistance gene Xa27, elicited a resistant reaction in the otherwise susceptible rice cultivar IR24. Four dTALE genes were made to induce the four annotated Xa27 homologous genes in rice cultivar Nipponbare, but none of the four induced Xa27-like genes conferred resistance to the dTALE-containing Xoo strains. A dTALE gene was also generated to activate the recessive resistance gene xa13, an allele of the disease-susceptibility gene Os8N3 (also named Xa13 or OsSWEET11, a member of sucrose efflux transporter SWEET gene family). The induction of xa13 by the dTALE rendered the resistant rice IRBB13 (xa13/xa13) susceptible to Xoo. Finally, OsSWEET12, an as-yet uncharacterized SWEET gene with no corresponding naturally occurring TAL effector identified, conferred susceptibility to the Xoo strains expressing the corresponding dTALE genes. Our results demonstrate that dTALEs can be delivered through the bacterial secretion system to activate genes of interest for functional analysis in plants.

Children and Psychotropic Medication: A Cautionary Note

ERIC Educational Resources Information Center

Morris, James; Stone, George

2011-01-01

This report addresses how the mental health field is organized in terms of the use of psychotropic medications with children and adolescents, and the ethical challenge this presents to marriage and family therapists.

Xanthomonas oryzae pv. oryzae TALE proteins recruit OsTFIIAγ1 to compensate for the absence of OsTFIIAγ5 in bacterial blight in rice.

PubMed

Ma, Wenxiu; Zou, Lifang; Ji, Zhiyuan; Xu, Xiameng; Xu, Zhengyin; Yang, Yangyang; Alfano, James R; Chen, Gongyou

2018-04-28

Xanthomonas oryzae pv. oryzae (Xoo), causal agent of bacterial blight (BB) of rice, uses transcription activator-like effectors (TALEs) to interact with the basal transcription factor gama subunit OsTFIIAγ5 (Xa5) and activates transcription of host genes. However, how OsTFIIAγ1, the other OsTFIIAγ protein, functions in the presence of TALEs remains unclear. In this study, we show that OsTFIIAγ1 plays a compensatory role in the absence of Xa5. The expression of OsTFIIAγ1, which is activated by TALE PthXo7, increased the expression of host genes targeted by avirulent and virulent TALEs. Defective OsTFIIAγ1 rice lines showed reduced expression of the TALE-targeted susceptibility (S) genes, OsSWEET11 and OsSWEET14, which resulted in increased BB resistance. Selected TALEs (PthXo1, AvrXa7, and AvrXa27) were evaluated for interactions with OsTFIIAγ1, Xa5 and xa5 (naturally-occurring mutant form of Xa5) using biomolecular fluorescence complementation (BiFC) and microscale thermophoresis (MST). BiFC and MST demonstrated that the three TALEs bind Xa5 and OsTFIIAγ1 with a stronger affinity than xa5. These results provide insight into the complex roles of OsTFIIAγ1 and OsTFIIAγ5 in TALE-mediated host gene transcription. This article is protected by copyright. All rights reserved. © 2018 BSPP and John Wiley & Sons Ltd.

A Conserved Basal Transcription Factor Is Required for the Function of Diverse TAL Effectors in Multiple Plant Hosts.

PubMed

Huang, Renyan; Hui, Shugang; Zhang, Meng; Li, Pei; Xiao, Jinghua; Li, Xianghua; Yuan, Meng; Wang, Shiping

2017-01-01

Many Xanthomonas bacteria use transcription activator-like effector (TALE) proteins to activate plant disease susceptibility ( S ) genes, and this activation contributes to disease. We recently reported that rice basal transcription factor IIA gamma subunit, OsTFIIAγ5, is hijacked by TALE-carrying Xanthomonas oryzae infecting the plants. However, whether TFIIAγs are also involved in TALE-carrying Xanthomonas -caused diseases in other plants is unknown. Here, molecular and genetic approaches were used to investigate the role of TFIIAγs in other plants. We found that TFIIAγs are also used by TALE-carrying Xanthomonas to cause disease in other plants. The TALEs of Xanthomonas citri pv. citri ( Xcc ) causing canker in citrus and Xanthomonas campestris pv. vesicatoria ( Xcv ) causing bacterial spot in pepper and tomato interacted with corresponding host TFIIAγs as in rice. Transcriptionally suppressing TFIIAγ led to resistance to Xcc in citrus and Xcv in pepper and tomato. The 39th residue of OsTFIIAγ5 and citrus CsTFIIAγ is vital for TALE-dependent induction of plant S genes. As mutated OsTFIIAγ5 V 39E , CsTFIIAγ V 39E , pepper CaTFIIAγ V 39E , and tomato SlTFIIAγ V 39E also did not interact with TALEs to prevent disease. These results suggest that TALE-carrying bacteria share a common mechanism for infecting plants. Using TFIIAγ V 39E -type mutation could be a general strategy for improving resistance to TALE-carrying pathogens in crops.

Quantitative analysis of TALE-DNA interactions suggests polarity effects.

PubMed

Meckler, Joshua F; Bhakta, Mital S; Kim, Moon-Soo; Ovadia, Robert; Habrian, Chris H; Zykovich, Artem; Yu, Abigail; Lockwood, Sarah H; Morbitzer, Robert; Elsäesser, Janett; Lahaye, Thomas; Segal, David J; Baldwin, Enoch P

2013-04-01

Transcription activator-like effectors (TALEs) have revolutionized the field of genome engineering. We present here a systematic assessment of TALE DNA recognition, using quantitative electrophoretic mobility shift assays and reporter gene activation assays. Within TALE proteins, tandem 34-amino acid repeats recognize one base pair each and direct sequence-specific DNA binding through repeat variable di-residues (RVDs). We found that RVD choice can affect affinity by four orders of magnitude, with the relative RVD contribution in the order NG > HD ≈ NN > NI > NK. The NN repeat preferred the base G over A, whereas the NK repeat bound G with 10(3)-fold lower affinity. We compared AvrBs3, a naturally occurring TALE that recognizes its target using some atypical RVD-base combinations, with a designed TALE that precisely matches 'standard' RVDs with the target bases. This comparison revealed unexpected differences in sensitivity to substitutions of the invariant 5'-T. Another surprising observation was that base mismatches at the 5' end of the target site had more disruptive effects on affinity than those at the 3' end, particularly in designed TALEs. These results provide evidence that TALE-DNA recognition exhibits a hitherto un-described polarity effect, in which the N-terminal repeats contribute more to affinity than C-terminal ones.

A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria.

PubMed

Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

2016-07-29

Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens.

Wildland-urban interface maps vary with purpose and context

USGS Publications Warehouse

Stewart, S.I.; Wilmer, B.; Hammer, R.B.; Aplet, G.H.; Hawbaker, T.J.; Miller, C.; Radeloff, V.C.

2009-01-01

Maps of the wildland-urban interface (WUI) are both policy tools and powerful visual images. Although the growing number of WUI maps serve similar purposes, this article indicates that WUI maps derived from the same data sets can differ in important ways related to their original intended application. We discuss the use of ancillary data in modifying census data to improve WUI maps and offer a cautionary note about this practice. A comparison of two WUI mapping approaches suggests that no single map is "best" because users' needs vary. The analysts who create maps are responsible for ensuring that users understand their purpose, data, and methods; map users are responsible for paying attention to these features and using each map accordingly. These considerations should apply to any analysis but are especially important to analyses of the WUI on which policy decisions will be made.

[Development of a Japanese version of the TALE scale].

PubMed

Ochiai, Tsutomu; Oguchi, Takashi

2013-12-01

The Thinking About Life Experiences (TALE) Scale (Bluck & Alea, 2011) has three subscales that assess the self, social, and directive functions of autobiographical memory. This study constructs a Japanese version of the TALE Scale and examines its reliability and validity. Fifteen items that assess the three functions of autobiographical memory were translated into Japanese. We conducted an online investigation with 600 men and women between 20-59 years of age. In Study 1, exploratory and confirmatory factor analysis identified that the three-factor structure of the Japanese version of the TALE Scale was the same as the original TALE Scale. Sufficient internal consistency of the scale was found, and the construct validity of the scale was supported by correlation analysis. Study 2 confirmed that the test-retest reliabilities of the three subscales were sufficient. Thus, this Japanese version of the TALE Scale is useful to assess autobiographical memory functions in Japan.

Improved specificity of TALE-based genome editing using an expanded RVD repertoire.

PubMed

Miller, Jeffrey C; Zhang, Lei; Xia, Danny F; Campo, John J; Ankoudinova, Irina V; Guschin, Dmitry Y; Babiarz, Joshua E; Meng, Xiangdong; Hinkley, Sarah J; Lam, Stephen C; Paschon, David E; Vincent, Anna I; Dulay, Gladys P; Barlow, Kyle A; Shivak, David A; Leung, Elo; Kim, Jinwon D; Amora, Rainier; Urnov, Fyodor D; Gregory, Philip D; Rebar, Edward J

2015-05-01

Transcription activator-like effector (TALE) proteins have gained broad appeal as a platform for targeted DNA recognition, largely owing to their simple rules for design. These rules relate the base specified by a single TALE repeat to the identity of two key residues (the repeat variable diresidue, or RVD) and enable design for new sequence targets via modular shuffling of these units. A key limitation of these rules is that their simplicity precludes options for improving designs that are insufficiently active or specific. Here we address this limitation by developing an expanded set of RVDs and applying them to improve the performance of previously described TALEs. As an extreme example, total conversion of a TALE nuclease to new RVDs substantially reduced off-target cleavage in cellular studies. By providing new RVDs and design strategies, these studies establish options for developing improved TALEs for broader application across medicine and biotechnology.

A transcription activator-like effector (TALE) induction system mediated by proteolysis.

PubMed

Copeland, Matthew F; Politz, Mark C; Johnson, Charles B; Markley, Andrew L; Pfleger, Brian F

2016-04-01

Simple and predictable trans-acting regulatory tools are needed in the fields of synthetic biology and metabolic engineering to build complex genetic circuits and optimize the levels of native and heterologous gene products. Transcription activator-like effectors (TALEs) are bacterial virulence factors that have recently gained traction in biotechnology applications owing to their customizable DNA-binding specificity. In this work we expanded the versatility of these transcription factors to create an inducible TALE system by inserting tobacco-etch virus (TEV) protease recognition sites into the TALE backbone. The resulting engineered TALEs maintain transcriptional repression of their target genes in Escherichia coli, but are degraded after induction of the TEV protease, thereby promoting expression of the previously repressed target gene of interest. This TALE-TEV technology enables both repression and induction of plasmid or chromosomal target genes in a manner analogous to traditional repressor proteins but with the added flexibility of being operator-agnostic.

TALE-mediated modulation of transcriptional enhancers in vivo.

PubMed

Crocker, Justin; Stern, David L

2013-08-01

We tested whether transcription activator-like effectors (TALEs) could mediate repression and activation of endogenous enhancers in the Drosophila genome. TALE repressors (TALERs) targeting each of the five even-skipped (eve) stripe enhancers generated repression specifically of the focal stripes. TALE activators (TALEAs) targeting the eve promoter or enhancers caused increased expression primarily in cells normally activated by the promoter or targeted enhancer, respectively. This effect supports the view that repression acts in a dominant fashion on transcriptional activators and that the activity state of an enhancer influences TALE binding or the ability of the VP16 domain to enhance transcription. In these assays, the Hairy repression domain did not exhibit previously described long-range transcriptional repression activity. The phenotypic effects of TALER and TALEA expression in larvae and adults are consistent with the observed modulations of eve expression. TALEs thus provide a novel tool for detection and functional modulation of transcriptional enhancers in their native genomic context.

Evaluating the Factor Structure of "Self-Concept" in Children: A Cautionary Note

ERIC Educational Resources Information Center

Drummond, Robert J.; McIntire, Walter G.

1977-01-01

This article examines the factor structure of two measures of self-concept routinely used with elementary school children: the Coopersmith Self-Esteem Inventory and the Self-Concept and Motivation Inventory. (Author)

HOXA1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on HOXA1 targets

PubMed Central

De Kumar, Bony; Parker, Hugo J.; Paulson, Ariel; Parrish, Mark E.; Pushel, Irina; Singh, Narendra Pratap; Zhang, Ying; Slaughter, Brian D.; Unruh, Jay R.; Florens, Laurence; Zeitlinger, Julia; Krumlauf, Robb

2017-01-01

Hoxa1 has diverse functional roles in differentiation and development. We identify and characterize properties of regions bound by HOXA1 on a genome-wide basis in differentiating mouse ES cells. HOXA1-bound regions are enriched for clusters of consensus binding motifs for HOX, PBX, and MEIS, and many display co-occupancy of PBX and MEIS. PBX and MEIS are members of the TALE family and genome-wide analysis of multiple TALE members (PBX, MEIS, TGIF, PREP1, and PREP2) shows that nearly all HOXA1 targets display occupancy of one or more TALE members. The combinatorial binding patterns of TALE proteins define distinct classes of HOXA1 targets, which may create functional diversity. Transgenic reporter assays in zebrafish confirm enhancer activities for many HOXA1-bound regions and the importance of HOX-PBX and TGIF motifs for their regulation. Proteomic analyses show that HOXA1 physically interacts on chromatin with PBX, MEIS, and PREP family members, but not with TGIF, suggesting that TGIF may have an independent input into HOXA1-bound regions. Therefore, TALE proteins appear to represent a wide repertoire of HOX cofactors, which may coregulate enhancers through distinct mechanisms. We also discover extensive auto- and cross-regulatory interactions among the Hoxa1 and TALE genes, indicating that the specificity of HOXA1 during development may be regulated though a complex cross-regulatory network of HOXA1 and TALE proteins. This study provides new insight into a regulatory network involving combinatorial interactions between HOXA1 and TALE proteins. PMID:28784834

An engineered promoter driving expression of a microbial avirulence gene confers recognition of TAL effectors and reduces growth of diverse Xanthomonas strains in citrus.

PubMed

Shantharaj, Deepak; Römer, Patrick; Figueiredo, Jose F L; Minsavage, Gerald V; Krönauer, Christina; Stall, Robert E; Moore, Gloria A; Fisher, Latanya C; Hu, Yang; Horvath, Diana M; Lahaye, Thomas; Jones, Jeffrey B

2017-09-01

Xanthomonas citri ssp. citri (X. citri), causal agent of citrus canker, uses transcription activator-like effectors (TALEs) as major pathogenicity factors. TALEs, which are delivered into plant cells through the type III secretion system (T3SS), interact with effector binding elements (EBEs) in host genomes to activate the expression of downstream susceptibility genes to promote disease. Predictably, TALEs bind EBEs in host promoters via known combinations of TALE amino acids to DNA bases, known as the TALE code. We introduced 14 EBEs, matching distinct X. citri TALEs, into the promoter of the pepper Bs3 gene (ProBs3 1EBE ), and fused this engineered promoter with multiple EBEs (ProBs3 14EBE ) to either the β-glucuronidase (GUS) reporter gene or the coding sequence (cds) of the pepper gene, Bs3. TALE-induced expression of the Bs3 cds in citrus leaves resulted in no visible hypersensitive response (HR). Therefore, we utilized a different approach in which ProBs3 1EBE and ProBs3 14EBE were fused to the Xanthomonas gene, avrGf1, which encodes a bacterial effector that elicits an HR in grapefruit and sweet orange. We demonstrated, in transient assays, that activation of ProBs3 14EBE by X. citri TALEs is T3SS dependent, and that the expression of AvrGf1 triggers HR and correlates with reduced bacterial growth. We further demonstrated that all tested virulent X. citri strains from diverse geographical locations activate ProBs3 14EBE . TALEs are essential for the virulence of X. citri strains and, because the engineered promoter traps are activated by multiple TALEs, this concept has the potential to confer broad-spectrum, durable resistance to citrus canker in stably transformed plants. © 2016 BSPP AND JOHN WILEY & SONS LTD.

Direct observation of transcription activator-like effector (TALE) protein dynamics

NASA Astrophysics Data System (ADS)

Cuculis, Luke; Abil, Zhanar; Zhao, Huimin; Schroeder, Charles M.

2014-03-01

In this work, we describe a single molecule assay to probe the site-search dynamics of transcription activator-like effector (TALE) proteins along DNA. In modern genetics, the ability to selectively edit the human genome is an unprecedented development, driven by recent advances in targeted nuclease proteins. Specific gene editing can be accomplished using TALE proteins, which are programmable DNA-binding proteins that can be fused to a nuclease domain. In this way, TALENs are a leading technology that has shown great success in the genomic editing of pluripotent stem cells. A major hurdle facing clinical implementation, however, is the potential for deleterious off-target binding events. For these reasons, a molecular-level understanding of TALE binding and target sequence search on DNA is essential. To this end, we developed a single-molecule fluorescence imaging assay that provides a first-of-its-kind view of the 1-D diffusion of TALE proteins along stretched DNA. Taken together with co-crystal structures of DNA-bound TALEs, our results suggest a rotationally-coupled, major groove tracking model for diffusion. We further report diffusion constants for TALE proteins as a function of salt concentration, consistent with previously described models of 1-D protein diffusion.

Two- and three-input TALE-based AND logic computation in embryonic stem cells.

PubMed

Lienert, Florian; Torella, Joseph P; Chen, Jan-Hung; Norsworthy, Michael; Richardson, Ryan R; Silver, Pamela A

2013-11-01

Biological computing circuits can enhance our ability to control cellular functions and have potential applications in tissue engineering and medical treatments. Transcriptional activator-like effectors (TALEs) represent attractive components of synthetic gene regulatory circuits, as they can be designed de novo to target a given DNA sequence. We here demonstrate that TALEs can perform Boolean logic computation in mammalian cells. Using a split-intein protein-splicing strategy, we show that a functional TALE can be reconstituted from two inactive parts, thus generating two-input AND logic computation. We further demonstrate three-piece intein splicing in mammalian cells and use it to perform three-input AND computation. Using methods for random as well as targeted insertion of these relatively large genetic circuits, we show that TALE-based logic circuits are functional when integrated into the genome of mouse embryonic stem cells. Comparing construct variants in the same genomic context, we modulated the strength of the TALE-responsive promoter to improve the output of these circuits. Our work establishes split TALEs as a tool for building logic computation with the potential of controlling expression of endogenous genes or transgenes in response to a combination of cellular signals.

A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria

PubMed Central

Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

2016-01-01

Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens. DOI: http://dx.doi.org/10.7554/eLife.19605.001 PMID:27472897

Assembly of Customized TAL Effectors Through Advanced ULtiMATE System.

PubMed

Yang, Junjiao; Guo, Shengjie; Yuan, Pengfei; Wei, Wensheng

2016-01-01

Transcription activator-like effectors (TALEs) have been widely applied in gene targeting. Here we describe an advanced ULtiMATE (USER-based Ligation-Mediated Assembly of TAL Effector) system that utilizes USER fusion technique and archive of 512 tetramer templates to achieve highly efficient construction of TALEs, which takes only half a day to accomplish the assembly of any given TALE construct. This system is also suitable for large-scale assembly of TALENs and any other TALE-based constructions.

HOXA1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on HOXA1 targets.

PubMed

De Kumar, Bony; Parker, Hugo J; Paulson, Ariel; Parrish, Mark E; Pushel, Irina; Singh, Narendra Pratap; Zhang, Ying; Slaughter, Brian D; Unruh, Jay R; Florens, Laurence; Zeitlinger, Julia; Krumlauf, Robb

2017-09-01

Hoxa1 has diverse functional roles in differentiation and development. We identify and characterize properties of regions bound by HOXA1 on a genome-wide basis in differentiating mouse ES cells. HOXA1-bound regions are enriched for clusters of consensus binding motifs for HOX, PBX, and MEIS, and many display co-occupancy of PBX and MEIS. PBX and MEIS are members of the TALE family and genome-wide analysis of multiple TALE members (PBX, MEIS, TGIF, PREP1, and PREP2) shows that nearly all HOXA1 targets display occupancy of one or more TALE members. The combinatorial binding patterns of TALE proteins define distinct classes of HOXA1 targets, which may create functional diversity. Transgenic reporter assays in zebrafish confirm enhancer activities for many HOXA1-bound regions and the importance of HOX-PBX and TGIF motifs for their regulation. Proteomic analyses show that HOXA1 physically interacts on chromatin with PBX, MEIS, and PREP family members, but not with TGIF, suggesting that TGIF may have an independent input into HOXA1-bound regions. Therefore, TALE proteins appear to represent a wide repertoire of HOX cofactors, which may coregulate enhancers through distinct mechanisms. We also discover extensive auto- and cross-regulatory interactions among the Hoxa1 and TALE genes, indicating that the specificity of HOXA1 during development may be regulated though a complex cross-regulatory network of HOXA1 and TALE proteins. This study provides new insight into a regulatory network involving combinatorial interactions between HOXA1 and TALE proteins. © 2017 De Kumar et al.; Published by Cold Spring Harbor Laboratory Press.

Is Robin Hood Alive in Your Classroom?

ERIC Educational Resources Information Center

Royer, Sharon E.

2002-01-01

Considers whether the tales of Robin Hood should be presented as fact or fiction. Discusses the appropriateness of the tales for use in literature programs. Presents arguments for Robin Hood as fact and arguments for Robin Hood as fiction. Considers different versions of the tale. (SG)

Folk Tales, Fairy Tales, and History: Uses and Classification.

ERIC Educational Resources Information Center

Claremont, Francesca

1993-01-01

Compiles excerpts from two 1964 lectures that examine the use of folk and fairy tales for the teaching of prehistory, geography, and grammar. Provides a starting point for thinking about the power of literature as an integrating medium in the Montessori elementary classroom. (HTH)

TALE transcription factors during early development of the vertebrate brain and eye.

PubMed

Schulte, Dorothea; Frank, Dale

2014-01-01

Our brain's cognitive performance arises from the coordinated activities of billions of nerve cells. Despite a high degree of morphological and functional differences, all neurons of the vertebrate central nervous system (CNS) arise from a common field of multipotent progenitors. Cell fate specification and differentiation are directed by multistep processes that include inductive/external cues, such as the extracellular matrix or growth factors, and cell-intrinsic determinants, such as transcription factors and epigenetic modulators of proteins and DNA. Here we review recent findings implicating TALE-homeodomain proteins in these processes. Although originally identified as HOX-cofactors, TALE proteins also contribute to many physiological processes that do not require HOX-activity. Particular focus is, therefore, given to HOX-dependent and -independent functions of TALE proteins during early vertebrate brain development. Additionally, we provide an overview about known upstream and downstream factors of TALE proteins in the developing vertebrate brain and discuss general concepts of how TALE proteins function to modulate neuronal cell fate specification. Copyright © 2013 Wiley Periodicals, Inc.

Cracking under Pressure.

ERIC Educational Resources Information Center

Caudle, Melissa; Baiamonte, John

1996-01-01

Workplace violence has not bypassed schools. Stories are surfacing about disgruntled school employees threatening, attacking, and sometimes killing administrators. This article shows how school leaders can develop greater awareness of potential problems and design cautionary measures. Contributing factors, warning signs, legal consequences,…

Tall Tales of North America.

ERIC Educational Resources Information Center

Fresno City Unified School District, CA.

Designed for use in junior high school language arts classes, this learning activity packet introduces students to North American folklore. Selected readings cover Indian tales, real folk heroes (Davy Crockett and John Henry), imaginary folk heroes (Paul Bunyan and Pecos Bill), Black folk stories (Brer Rabbit), and tales of Washington Irving. Each…

Happily Ever After? Teens and Fairy Tales.

ERIC Educational Resources Information Center

Tuccillo, Diane P.

2001-01-01

Argues, from the author's experience and with supporting quotes from many teenagers, that modern retellings of classic fairy tales can be very popular with teenage readers. Discusses numerous such stories, and offers an extensive list of retold fairy tales, organized into: Cinderella stories, Beauty and the Beast stories, Sleeping Beauty stories,…

Reading, Writing, and "Rhythmetics" for the Verbally Gifted.

ERIC Educational Resources Information Center

Pilon, A. Barbara

The monograph presents a variety of language arts teaching ideas for use with gifted students. Teachers are encouraged to expose children to much literature including poetry, folk tales, riddles, fairy tales, "pourquoi" tales, myths and legends, fantasy, science fiction, and biographies and autobiographies. The document offers the SIMMER theory of…

Fairy Tales as a Cultural Context in the French Classroom.

ERIC Educational Resources Information Center

Obergfell, Sandra C.

1983-01-01

Discusses the use of fairy tales in intermediate and advanced French courses as source material for discussion of French cultural values and traditional behavior patterns. Methods of analyzing values in a fairy tale and implementation in the classroom are discussed using "Le Petit Chaperon Rouge" as an example. (AMH)

Recovering Native Traditions and Tales for Younger Readers.

ERIC Educational Resources Information Center

Stott, Jon C.

1995-01-01

Reviews 14 children's books concerned with traditional Native American tales and experiences, written mostly by Native authors and published 1989-93. Includes books on Hiawatha, buffalo, the battle of the Little Bighorn, the Fetterman Fight, and traditional beliefs and values; Cree, Navajo, Chickasaw, and Seneca tales and stories; fictional…

[Transcription activator-like effectors(TALEs)based genome engineering].

PubMed

Zhao, Mei-Wei; Duan, Cheng-Li; Liu, Jiang

2013-10-01

Systematic reverse-engineering of functional genome architecture requires precise modifications of gene sequences and transcription levels. The development and application of transcription activator-like effectors(TALEs) has created a wealth of genome engineering possibilities. TALEs are a class of naturally occurring DNA-binding proteins found in the plant pathogen Xanthomonas species. The DNA-binding domain of each TALE typically consists of tandem 34-amino acid repeat modules rearranged according to a simple cipher to target new DNA sequences. Customized TALEs can be used for a wide variety of genome engineering applications, including transcriptional modulation and genome editing. Such "genome engineering" has now been established in human cells and a number of model organisms, thus opening the door to better understanding gene function in model organisms, improving traits in crop plants and treating human genetic disorders.

TALE-PvuII fusion proteins--novel tools for gene targeting.

PubMed

Yanik, Mert; Alzubi, Jamal; Lahaye, Thomas; Cathomen, Toni; Pingoud, Alfred; Wende, Wolfgang

2013-01-01

Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA-cleavage module. This architecture is also used by TALE nucleases (TALENs), in which the DNA-binding modules of the ZFNs have been replaced by DNA-binding domains based on transcription activator like effector (TALE) proteins. Both TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI to induce double-strand DNA cleavage at the target site after recognition of the target DNA by the respective DNA-binding module. TALENs seem to have an advantage over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we present evidence that variant TALENs can be produced by replacing the catalytic domain of FokI with the restriction endonuclease PvuII. These fusion proteins recognize only the composite recognition site consisting of the target site of the TALE protein and the PvuII recognition sequence (addressed site), but not isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess of protein over DNA and long incubation times. In vitro, their preference for an addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion proteins are active in cellula with minimal cytotoxicity.

Girlhood, Sexual Violence, and Agency in Francesca Lia Block's "Wolf"

ERIC Educational Resources Information Center

Marshall, Elizabeth

2009-01-01

This essay examines the representation of adolescent girlhood, sexual violence and agency in Francesca Lia Block's contemporary fairy tale collection "The Rose and The Beast." Focusing specifically on the tale "Wolf," the author provides a literary analysis of how Block draws on and reworks traditional Western fairy tale variants to reintroduce…

Ladrillo and Tales of Juan Bobo: Puerto Rican Folk Tales.

ERIC Educational Resources Information Center

Matos, Reinaldo; Matos, Ana

These two illustrated elementary readers contain the Spanish and English versions of the Puerto Rican folk tales, "Ladrillo" and "Cuentos de Juan Bobo." They are part of a series of reading materials for elementary-level migrant children. These materials are intended to help the child relate to his culture, develop interest in…

E-Classical Fairy Tales: Multimedia Builder as a Tool

ERIC Educational Resources Information Center

Eteokleous, Nikleia; Ktoridou, Despo; Tsolakidis, Symeon

2011-01-01

The study examines pre-service teachers' experiences in delivering a traditional-classical fairy tale using the Multimedia Builder software, in other words an e-fairy tale. A case study approach was employed, collecting qualitative data through classroom observations and focus groups. The results focus on pre-service teachers' reactions, opinions,…

Normativity in Fairy Tales: Scope, Range and Modes of Communication

ERIC Educational Resources Information Center

Hohr, Hansjörg

2013-01-01

The article studies in three steps how the fairy tale articulates its normative content and what the educational consequence of this kind of communication is. First, the articulation of normativity in fictional literature in general is discussed. Second, the specific mode in which the fairy tale articulates its normativity is studied according to…

A Case Study of Editorial Filters in Folktales: A Discussion of the "Allerleirauh" Tales in Grimm.

ERIC Educational Resources Information Center

Dollerup, Cay; And Others

1986-01-01

This article discusses editorial "filters" in folktales, specifically the changes ("orientations") which editors deliberately impose on a tale because they want to reach a specific audience. A case in point is the tale called "Allerleirauh," in the Grimm collection, which not only is highly illustrative of editorial…

The Teaching of Chaucer in Fifth and Sixth Forms.

ERIC Educational Resources Information Center

Brew, Trevor

1967-01-01

The teacher can sucessfully present Chaucer's "Canterbury Tales" to 11th- and 12th-grade students by concentrating on "The Prologue" and one of the tales--e.g., "The Pardoner's Tale." The structure and plan of the entire work, however, should first be considered before its various parts can be fully understood.…

Larger than Life: Reading and Writing Tall Tales

ERIC Educational Resources Information Center

Tunks, Karyn

2008-01-01

The genre of tall tales is characterized by fictional, often intentionally ridiculous, stories that provide a reason for or origin of a natural phenomenon. Tall tales are often based on characters who are unusually adept or powerful; they are particularly appealing to children who are cognitively capable of understanding the tongue-in-cheek humor…

A multicolor panel of TALE-KRAB based transcriptional repressor vectors enabling knockdown of multiple gene targets

PubMed Central

Zhang, Zhonghui; Wu, Elise; Qian, Zhijian; Wu, Wen-Shu

2014-01-01

Stable and efficient knockdown of multiple gene targets is highly desirable for dissection of molecular pathways. Because it allows sequence-specific DNA binding, transcription activator-like effector (TALE) offers a new genetic perturbation technique that allows for gene-specific repression. Here, we constructed a multicolor lentiviral TALE-Kruppel-associated box (KRAB) expression vector platform that enables knockdown of multiple gene targets. This platform is fully compatible with the Golden Gate TALEN and TAL Effector Kit 2.0, a widely used and efficient method for TALE assembly. We showed that this multicolor TALE-KRAB vector system when combined together with bone marrow transplantation could quickly knock down c-kit and PU.1 genes in hematopoietic stem and progenitor cells of recipient mice. Furthermore, our data demonstrated that this platform simultaneously knocked down both c-Kit and PU.1 genes in the same primary cell populations. Together, our results suggest that this multicolor TALE-KRAB vector platform is a promising and versatile tool for knockdown of multiple gene targets and could greatly facilitate dissection of molecular pathways. PMID:25475013

Chimeric TALE recombinases with programmable DNA sequence specificity.

PubMed

Mercer, Andrew C; Gaj, Thomas; Fuller, Roberta P; Barbas, Carlos F

2012-11-01

Site-specific recombinases are powerful tools for genome engineering. Hyperactivated variants of the resolvase/invertase family of serine recombinases function without accessory factors, and thus can be re-targeted to sequences of interest by replacing native DNA-binding domains (DBDs) with engineered zinc-finger proteins (ZFPs). However, imperfect modularity with particular domains, lack of high-affinity binding to all DNA triplets, and difficulty in construction has hindered the widespread adoption of ZFPs in unspecialized laboratories. The discovery of a novel type of DBD in transcription activator-like effector (TALE) proteins from Xanthomonas provides an alternative to ZFPs. Here we describe chimeric TALE recombinases (TALERs): engineered fusions between a hyperactivated catalytic domain from the DNA invertase Gin and an optimized TALE architecture. We use a library of incrementally truncated TALE variants to identify TALER fusions that modify DNA with efficiency and specificity comparable to zinc-finger recombinases in bacterial cells. We also show that TALERs recombine DNA in mammalian cells. The TALER architecture described herein provides a platform for insertion of customized TALE domains, thus significantly expanding the targeting capacity of engineered recombinases and their potential applications in biotechnology and medicine.

A multicolor panel of TALE-KRAB based transcriptional repressor vectors enabling knockdown of multiple gene targets.

PubMed

Zhang, Zhonghui; Wu, Elise; Qian, Zhijian; Wu, Wen-Shu

2014-12-05

Stable and efficient knockdown of multiple gene targets is highly desirable for dissection of molecular pathways. Because it allows sequence-specific DNA binding, transcription activator-like effector (TALE) offers a new genetic perturbation technique that allows for gene-specific repression. Here, we constructed a multicolor lentiviral TALE-Kruppel-associated box (KRAB) expression vector platform that enables knockdown of multiple gene targets. This platform is fully compatible with the Golden Gate TALEN and TAL Effector Kit 2.0, a widely used and efficient method for TALE assembly. We showed that this multicolor TALE-KRAB vector system when combined together with bone marrow transplantation could quickly knock down c-kit and PU.1 genes in hematopoietic stem and progenitor cells of recipient mice. Furthermore, our data demonstrated that this platform simultaneously knocked down both c-Kit and PU.1 genes in the same primary cell populations. Together, our results suggest that this multicolor TALE-KRAB vector platform is a promising and versatile tool for knockdown of multiple gene targets and could greatly facilitate dissection of molecular pathways.

A TALE OF THREE MYSTERIOUS SPECTRAL FEATURES IN CARBON-RICH EVOLVED STARS: THE 21 μm, 30 μm, AND “UNIDENTIFIED INFRARED” EMISSION FEATURES

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

Mishra, Ajay; Li, Aigen; Jiang, B. W., E-mail: amishra@mail.missouri.edu, E-mail: lia@missouri.edu, E-mail: bjiang@bnu.edu.cn

2015-03-20

The mysterious “21 μm” emission feature seen almost exclusively in the short-lived protoplanetary nebula (PPN) phase of stellar evolution remains unidentified since its discovery two decades ago. This feature is always accompanied by the equally mysterious, unidentified “30 μm” feature and the so-called “unidentified infrared” (UIR) features at 3.3, 6.2, 7.7, 8.6, and 11.3 μm which are generally attributed to polycyclic aromatic hydrocarbon (PAH) molecules. The 30 μm feature is commonly observed in all stages of stellar evolution from the asymptotic giant branch through PPN to the planetary nebula phase. We explore the interrelations among the mysterious 21, 30 μm,more » and UIR features of the 21 μm sources. We derive the fluxes emitted in the observed UIR, 21, and 30 μm features from published Infrared Space Observatory or Spitzer/IRS spectra. We find that none of these spectral features correlate with each other. This argues against a common carrier (e.g., thiourea) for both the 21 μm feature and the 30 μm feature. This also does not support large PAH clusters as a possible carrier for the 21 μm feature.« less

It's No Secret: Fifty-eight Years of National Security Programs at BNL (463rd Brookhaven Lecture)

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

Indusi, Joseph

2010-11-17

Prepare for a true tale of suspense and international intrigue. A tale that began in 1952, continued through the Cold War, and is not yet complete today. A tale of unexpected allies. Hear the true tale of one Laboratory’s efforts to keep nuclear materials out of the hands of evildoers. Freidlander. Higinbotham. Dodson. Kouts. And many more! See some of BNL’s all-star cast in the defining roles that shaped their careers as they worked toward keeping the nation and the world safe from the proliferation of nuclear weapons.

TALE-PvuII Fusion Proteins – Novel Tools for Gene Targeting

PubMed Central

Yanik, Mert; Alzubi, Jamal; Lahaye, Thomas; Cathomen, Toni; Pingoud, Alfred; Wende, Wolfgang

2013-01-01

Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA-cleavage module. This architecture is also used by TALE nucleases (TALENs), in which the DNA-binding modules of the ZFNs have been replaced by DNA-binding domains based on transcription activator like effector (TALE) proteins. Both TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI to induce double-strand DNA cleavage at the target site after recognition of the target DNA by the respective DNA-binding module. TALENs seem to have an advantage over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we present evidence that variant TALENs can be produced by replacing the catalytic domain of FokI with the restriction endonuclease PvuII. These fusion proteins recognize only the composite recognition site consisting of the target site of the TALE protein and the PvuII recognition sequence (addressed site), but not isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess of protein over DNA and long incubation times. In vitro, their preference for an addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion proteins are active in cellula with minimal cytotoxicity. PMID:24349308

Using Fairy Tales to Change Perceptions of Self and Others.

ERIC Educational Resources Information Center

Gornicki, Sylvia B.

Fairy tales can be used in the classroom to promote normal growth and development as well as carry a message of hope and faith in the strength and goodness of humans. Because fairy tales are imaginative literature, readers can safely experience and work through scary situations which are analogous to situations in real life. Bibliotherapy refers…

The Indecisive Feminist: Study of Anne Sexton's Revisionist Fairy Tales

ERIC Educational Resources Information Center

Mohammed, Nadia Fayidh

2015-01-01

Fairy tales to female writers are major resource for their abundant writings, but for the feminist poets since 1960s, they become essential subject matter to often deal with in their literary production. With the motivation to address the conventional tradition of patriarchal society, and re-address the stereotype females inhabiting these tales,…

The Celebration of Death: Two Folk Tales about DEath. Mini-Module.

ERIC Educational Resources Information Center

African-American Inst., New York, NY. School Services Div.

This module contains two African folk tales about death, two descriptions of African funerals, a lesson plan with 11 questions exploring the finality of and customs surrounding death, and a bibliography of five books which deal with African religious beliefs. The folk tales present concepts of death and immortality of the soul. The descriptions of…

Understanding "A Tale of Two Cities": A Student Casebook to Issues, Sources, and Historical Documents.

ERIC Educational Resources Information Center

Newlin, George

Charles Dickens' novel, "A Tale of Two Cities," does not waste a word in telling a touching, suspenseful tale set against the background of one of the bloodiest events in history, the French Revolution. This casebook's collection of historical documents, collateral readings, and commentary will promote interdisciplinary study of the…

Spinning New Tales from Traditional Texts: Donna Jo Napoli and the Rewriting of Fairy Tale.

ERIC Educational Resources Information Center

Crew, Hilary S.

2002-01-01

Demonstrates how Donna Jo Napoli changes generic conventions and reworks discursive formations in order to retell tradition tales. Discusses the narrative strategies she uses in telling her stories, her representation of male and female characters in regard to gender and gendered relationships, and the way she renegotiates ideologies and value…

Composing Storied Ground: Four Generations of Narrative Inquiry

ERIC Educational Resources Information Center

Schaafsma, David; Pagnucci, Gian; Wallace, Rob; Stock, Patricia Lambert

2007-01-01

Narrative inquiry in English education comes in many shapes and forms--tales of classrooms and communities, didactic argu-stories, postmodern pastiches, open tales with O. Henry endings--but the heart of the enterprise is research in the form of story or, in other words, exploring the world by telling a story about it. In many such tales, all of…

Folktale Frenzy: WebQuest Writing.

ERIC Educational Resources Information Center

Gaines, Lisa

This folktale unit supports 6th- through 8th-grade students exploration of the many subgenres of folktales: trickster tales, fairy tales, fables, tall tales, and legends. The unit focuses heavily on the use of technology as a learning tool as students work together to create WebQuests for their peers to explore. During the 10 one-hour sessions,…

Fairy Tales of the Sea [and] A Guide for Teachers.

ERIC Educational Resources Information Center

Cowan, Elizabeth, Comp.; And Others

Presented are 25 fairy tales from around the world that are related to the sea. Included in the teacher's guide are activities designed to serve as a catalyst to stimulate varied classroom uses for the tales. The curriculum outline provided follows the English Language Arts Curriculum Framework suggested by the Texas Education Agency and covers…

Engaging with Mathematics in the Kindergarten. Orchestrating a Fairy Tale through Questioning and Use of Tools

ERIC Educational Resources Information Center

Carlsen, Martin

2013-01-01

The aim of this study is to analyse how a kindergarten teacher orchestrated a mathematical activity involving a fairy tale. Taking a sociocultural perspective on learning and development, naturally occurring talk-in-interaction has been analysed in order to scrutinise the subtleties of the orchestration. The fairy tale "Goldilocks and the…

Fairy Tales and Foreign Languages: Ever the Twain Shall Meet

ERIC Educational Resources Information Center

Davidheiser, James C.

2007-01-01

Fairy tales are not new to foreign language instructors, but on occasion they have been considered wither exoteric or unworthy of class time. Yet today there is a resurgence of interest in fairy tales and a rebirth of their use in the arts, which may serve foreign language instructors. This article presents historical background to inform…

Forever Acting Alone: The Absence of Female Collaboration in "Grimms' Fairy Tales."

ERIC Educational Resources Information Center

Mendelson, Michael

1997-01-01

Explores the roles allocated to women in the famous collection. States that, although collaboration figures prominently in many of the more than 200 tales, the benefits of collective action are not extended to women. Examines the differences between male and female collaboration in the tales. Contemplates the implications of these differences for…

The Fantastic Tale for Children: Its Literary and Educational Problems.

ERIC Educational Resources Information Center

Klingberg, Goete

1967-01-01

The fantastic tale is a genre of children's literature in which magic and reality are found side by side in a superficially plausible story with a definite historical setting. Motifs characteristic of the tale are living toys, strange children, modern witches, space and time displacements, "doors" to the wonderland, the mythical world itself, and…

Resurrecting the buried self: fairy tales and the analytic encounter.

PubMed

Jacobs, Linda

2011-12-01

The author uses the lens of myth and fairy tales to examine the narratives generated by the analytic experience. Fairy tales are understood as representing fundamental developmental conflicts, accounting for their enduring power over time. The analytic encounter is seen as an analogue of the fairy tale in which the hidden self, damaged by loss and abandonment, reemerges only through the redemptive power of [an] other's love. Clinical material is presented in which hidden parts of the patient's self are projected into the analyst for safekeeping; these hidden parts resonate with the analyst's own lost, unrealized potential and form an intersubjective experience which the author believes is transformative. The patient's dormant powers emerge in a newly experienced atmosphere of recognition, and in this way, the analytic encounter resembles the fairy tale in providing an identificatory bond and a protective space for the patient's hidden vitality.

Telescope Array Low energy Extension: TALE

NASA Astrophysics Data System (ADS)

Ogio, Shoichi

TALE, the Telescope Array Low Energy extension was designed to lower the energy threshold to about 1016.5 eV. TALE has a surface detector (SD) array made up of 103 scintillation counters (40 with 400 m spacing, 36 with 600 m spacing and 27 with 1.2 km spacing) and a Fluorescence Detector (FD) station consisting of ten FD telescopes working with the Telescope Array Middle Drum FD station, which is made up of 14 telescopes. TALE-FD full operation started in 2013 and the SD array was partially-completed with 16 SDs and continues the operation from 2014. We will describe the history and the current status of the detectors and will make a brief report about the FD and the hybrid analysis results. TALE detector will be completed as a hybrid air shower detector in 2018. We will report the technical details of the detectors, the schedule and the expected performances.

Engineered TAL Effector modulators for the large-scale gain-of-function screening

PubMed Central

Zhang, Hanshuo; Li, Juan; Hou, Sha; Wang, Gancheng; Jiang, Mingjun; Sun, Changhong; Hu, Xiongbing; Zhuang, Fengfeng; Dai, Zhifei; Dai, Junbiao; Xi, Jianzhong Jeff

2014-01-01

Recent effective use of TAL Effectors (TALEs) has provided an important approach to the design and synthesis of sequence-specific DNA-binding proteins. However, it is still a challenging task to design and manufacture effective TALE modulators because of the limited knowledge of TALE–DNA interactions. Here we synthesized more than 200 TALE modulators and identified two determining factors of transcription activity in vivo: chromatin accessibility and the distance from the transcription start site. The implementation of these modulators in a gain-of-function screen was successfully demonstrated for four cell lines in migration/invasion assays and thus has broad relevance in this field. Furthermore, a novel TALE–TALE modulator was developed to transcriptionally inhibit target genes. Together, these findings underscore the huge potential of these TALE modulators in the study of gene function, reprogramming of cellular behaviors, and even clinical investigation. PMID:24939900

Application of TALE-Based Approach for Dissecting Functional MicroRNA-302/367 in Cellular Reprogramming.

PubMed

Zhang, Zhonghui; Wu, Wen-Shu

2018-01-01

MicroRNAs are small 18-24 nt single-stranded noncoding RNA molecules involved in many biological processes, including stemness maintenance and cellular reprogramming. Current methods used in loss-of-function studies of microRNAs have several limitations. Here, we describe a new approach for dissecting miR-302/367 functions by transcription activator-like effectors (TALEs), which are natural effector proteins secreted by Xanthomonas and Ralstonia bacteria. Knockdown of the miR-302/367 cluster uses the Kruppel-associated box repressor domain fused with specific TALEs designed to bind the miR-302/367 cluster promoter. Knockout of the miR-302/367 cluster uses two pairs of TALE nucleases (TALENs) to delete the miR-302/367 cluster in human primary cells. Together, both TALE-based transcriptional repressor and TALENs are two promising approaches for loss-of-function studies of microRNA cluster in human primary cells.

A transcription activator-like effector induction system mediated by proteolysis

PubMed Central

Copeland, Matthew F.; Politz, Mark C.; Johnson, Charles B.; Markley, Andrew L.; Pfleger, Brian F.

2016-01-01

Simple and predictable trans-acting regulatory tools are needed in the fields of synthetic biology and metabolic engineering to build complex genetic circuits and optimize the levels of native and heterologous gene products. Transcription activator-like effectors (TALEs) are bacterial virulence factors that have recently gained traction in biotechnology applications due to their customizable DNA binding specificity. In this work we expand the versatility of these transcription factors to create an inducible TALE system by inserting tobacco-etch virus (TEV) protease recognition sites into the TALE backbone. The resulting engineered TALEs maintain transcriptional repression of their target genes in Escherichia coli, but are degraded following the induction of the TEV protease, thereby promoting expression of the previously repressed target gene of interest. This TALE-TEV technology enables both repression and induction of plasmid or chromosomal target genes in a manner analogous to traditional repressor proteins but with the added flexibility of being operator agnostic. PMID:26854666

To Be Specific or Not: The Critical Relationship Between Hox And TALE Proteins.

PubMed

Merabet, Samir; Mann, Richard S

2016-06-01

Hox proteins are key regulatory transcription factors that act in different tissues of the embryo to provide specific spatial and temporal coordinates to each cell. These patterning functions often depend on the presence of the TALE-homeodomain class cofactors, which form cooperative DNA-binding complexes with all Hox proteins. How this family of cofactors contributes to the highly diverse and specific functions of Hox proteins in vivo remains an important unsolved question. We review here the most recent advances in understanding the molecular mechanisms underlying Hox-TALE function. In particular, we discuss the role of DNA shape, DNA-binding affinity, and protein-protein interaction flexibility in dictating Hox-TALE specificity. We propose several models to explain how these mechanisms are integrated with each other in the context of the many distinct functions that Hox and TALE factors carry out in vivo. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Study on Choosing Tales for Utilising as Teaching Materials in Turkish Language Education

ERIC Educational Resources Information Center

Ayranci, Bilge Bagci

2017-01-01

Fairy tales are used intensively by Turkish teachers in Turkish lessons. Elements in tales need to be examined in many respects such as their suitability for cultural transmission, psychological benefits, and harms, correct and effective use of language and so on. The opinions of the Turkish teachers in the field are very important for this…

The Monets, Van Goghs, and Renoirs of Science Education: Writing Impressionist Tales as a Strategy for Facilitating Prospective Teachers' Reflections on Science Experiences

ERIC Educational Resources Information Center

Bryan, Lynn A.; Tippins, Deborah J.

2005-01-01

A particularly useful pedagogical strategy for beginning a dialogue with prospective teachers about the ways in which their experiences and beliefs shape their development of professional knowledge is writing impressionist tales. Impressionist tales are a form of autobiography that portrays one highly personal perspective on a significant moment…

The Therapeutic Use of Fairy Tales with Adults in Group Therapy

ERIC Educational Resources Information Center

Brown, Nina W.

2007-01-01

Fairy tales are not just for children. They can hold important messages for people of all ages, as well as for those with special needs. For example, people who present for therapy reporting such issues as fear of abandonment, sibling rivalry, self-esteem, and lack of meaning in life, among others, can benefit from using fairy tales as a…

It's No Secret: Fifty-eight Years of National Security Programs at BNL (463rd Brookhaven Lecture)

ScienceCinema

Indusi, Joseph [BNL Nonproliferation and National Security Department

2017-12-09

Prepare for a true tale of suspense and international intrigue. A tale that began in 1952, continued through the Cold War, and is not yet complete today. A tale of unexpected allies. Hear the true tale of one Laboratory’s efforts to keep nuclear materials out of the hands of evildoers. Freidlander. Higinbotham. Dodson. Kouts. And many more! See some of BNL’s all-star cast in the defining roles that shaped their careers as they worked toward keeping the nation and the world safe from the proliferation of nuclear weapons.

Direct regulation of E-cadherin by targeted histone methylation of TALE-SET fusion protein in cancer cells.

PubMed

Cho, Hyun-Soo; Kang, Jeong Gu; Lee, Jae-Hye; Lee, Jeong-Ju; Jeon, Seong Kook; Ko, Jeong-Heon; Kim, Dae-Soo; Park, Kun-Hyang; Kim, Yong-Sam; Kim, Nam-Soon

2015-09-15

TALE-nuclease chimeras (TALENs) can bind to and cleave specific genomic loci and, are used to engineer gene knockouts and additions. Recently, instead of using the FokI domain, epigenetically active domains, such as TET1 and LSD1, have been combined with TAL effector domains to regulate targeted gene expression via DNA and histone demethylation. However, studies of histone methylation in the TALE system have not been performed. Therefore, in this study, we established a novel targeted regulation system with a TAL effector domain and a histone methylation domain. To construct a TALE-methylation fusion protein, we combined a TAL effector domain containing an E-Box region to act as a Snail binding site and the SET domain of EHMT 2 to allow for histone methylation. The constructed TALE-SET module (TSET) repressed the expression of E-cadherin via by increasing H3K9 dimethylation. Moreover, the cells that overexpressed TSET showed increased cell migration and invasion. This is the first phenotype-based study of targeted histone methylation by the TALE module, and this new system can be applied in new cancer therapies to reduce side effects.

Mentoring: Some cautionary notes for the nursing profession.

PubMed

Green, Janet; Jackson, Debra

2013-12-21

Abstract Mentoring has been embraced in nursing as a way of socialising new nurses into the profession, growing and developing nursing talent, and more recently as a way to retain experienced nurses with the current nursing shortage. Much of the extant literature focusses on the benefits of mentoring, differences between formal and informal mentoring, the elements of a successful mentoring relationship, and the characteristics of 'good' mentors and protégées. Until recently the research on mentoring has almost exclusively focused on the positive aspects of mentoring for the protégées, organisations and to a lesser extent, mentors. While viewed by many as a beneficial and enriching developmental experience, it is equally important to recognise that there can be a darker side to the mentoring experience for the mentor and protégée. This paper will explore the negative aspects associated with mentoring and mentoring relationships and provide some cautionary notes for nursing.

Mentoring: Some cautionary notes for the nursing profession.

PubMed

Green, Janet; Jackson, Debra

2014-01-01

Abstract Mentoring has been embraced in nursing as a way of socialising new nurses into the profession, growing and developing nursing talent, and more recently as a way to retain experienced nurses with the current nursing shortage. Much of the extant literature focusses on the benefits of mentoring, differences between formal and informal mentoring, the elements of a successful mentoring relationship, and the characteristics of 'good' mentors and protégées. Until recently the research on mentoring has almost exclusively focussed on the positive aspects of mentoring for the protégées, organisations and to a lesser extent, mentors. While viewed by many as a beneficial and enriching developmental experience, it is equally important to recognise that there can be a darker side to the mentoring experience for the mentor and protégée. This paper will explore the negative aspects associated with mentoring and mentoring relationships and provide some cautionary notes for nursing.

Xanthomonas TAL effectors hijack host basal transcription factor IIA α and γ subunits for invasion.

PubMed

Ma, Ling; Wang, Qiang; Yuan, Meng; Zou, Tingting; Yin, Ping; Wang, Shiping

2018-02-05

The Xanthomonas genus includes Gram-negative plant-pathogenic bacteria, which infect a broad range of crops and wild plant species, cause symptoms with leaf blights, streaks, spots, stripes, necrosis, wilt, cankers and gummosis on leaves, stems and fruits in a wide variety of plants via injecting their effector proteins into the host cell during infection. Among these virulent effectors, transcription activator-like effectors (TALEs) interact with the γ subunit of host transcription factor IIA (TFIIAγ) to activate the transcription of host disease susceptibility genes. Functional TFIIA is a ternary complex comprising α, β and γ subunits. However, whether TALEs recruit TFIIAα, TFIIAβ, or both remains unknown. The underlying molecular mechanisms by which TALEs mediate host susceptibility gene activation require full elucidation. Here, we show that TALEs interact with the α+γ binary subcomplex but not the α+β+γ ternary complex of rice TFIIA (holo-OsTFIIA). The transcription factor binding (TFB) regions of TALEs, which are highly conserved in Xanthomonas species, have a dominant role in these interactions. Furthermore, the interaction between TALEs and the α+γ complex exhibits robust DNA binding activity in vitro. These results collectively demonstrate that TALE-carrying pathogens hijack the host basal transcription factors TFIIAα and TFIIAγ, but not TFIIAβ, to enhance host susceptibility during pathogen infection. The uncovered mechanism widens new insights on host-microbe interaction and provide an applicable strategy to breed high-resistance crop varieties. Copyright © 2018 Elsevier Inc. All rights reserved.

Case Series in Cognitive Neuropsychology: Promise, Perils and Proper Perspective

PubMed Central

Rapp, Brenda

2012-01-01

Schwartz & Dell (2010) advocated for a major role for case series investigations in cognitive neuropsychology. They defined the key features of this approach and presented a number of arguments and examples illustrating the benefits of case series studies and their contribution to computational cognitive neuropsychology. In the Special Issue on “Case Series in Cognitive Neuropsychology” there are six commentaries on Schwartz and Dell (2010) as well as a response to the six commentaries by Dell and Schwartz. In this paper, I provide a brief summary of the key points made in Schwartz and Dell (2010) and I review the promise and perils of case series design as revealed by the six commentaries. I conclude by placing the set of papers within a broader perspective, providing some clarification of the historical record on case series and single case approaches, raising some cautionary notes for case series studies and situating both case series and single case approaches within the larger context of theory development in the cognitive sciences. PMID:22746685

Cigarette Excise Taxes in Context: Cautionary Lessons from the U.S. Experience.

PubMed

Campbell, Richard B; Balbach, Edith D

2015-01-01

Cigarette excise taxes are an important tool in the World Health Organization Framework Convention on Tobacco Control strategy for reducing global tobacco consumption. However, contemporary tobacco control efforts also coincide with the proliferation of neoliberal economic programs calling for the withdrawal of state activity from the economy to facilitate trade. In this environment, cigarette excise taxes may be seen less as an instrument of tobacco control than a feature of an economic program that is punitive to lower-income people. This article reviews collaboration between progressive organizations in the United States and the tobacco industry in the 1980s and 1990s, documenting potential sources of unanticipated resistance to excise taxes and highlighting the tobacco industry's capacity to engage in policy issues through third-party surrogates. It is important for those implementing cigarette excise tax increases to distance tobacco control objectives from larger economic policy measures and for tobacco control advocates to build alliances with organizations working for economic fairness in order to address mutual concerns. © SAGE Publications 2015.

Oral Interpretation of C.S. Lewis'"Narnia Tales": A Refracting of "Pictures."

ERIC Educational Resources Information Center

Keefe, Carolyn

"The Chronicles of Narnia" are a series of seven fairy tales written by C.S. Lewis that have become popular with both children and adults. Lewis points to five aspects of the fairy tale form that made the form suitable for expressing the images he saw. The aspects are: (1) no love interest; (2) no close psychology; (3) severe restraints…

Fairy Tales and Fantasy: Bridges to Literature--Using Fairy Tales and Fantasy to Motivate the Reluctant Reader.

ERIC Educational Resources Information Center

Dungey, Joan M.

Designed to give children a sense of the cultural heritage that fairy tales represent, this instructional unit was originally developed to motivate eighth-grade low-level readers and was later adapted for English as a second language classes and for a variety of elementary and secondary school learning levels. Objectives of the unit are to help…

Survey on Effects of Fairy Tales on Turkish Language Training from Secondary School Students' Perspective

ERIC Educational Resources Information Center

Kiliç, Yasin

2015-01-01

Fairy tale is one of the most important genres in literature which reflects childish sensitivity, feeds child's soul, enriches his/her imagination and prepares him/her for the future. Emerging as product of oral literature, fairy tales were used as an instrument of training in the past and they still have the same function today. Educators think…

Understanding the Psychology of a Trickster Tale: 5-Year-Old Japanese Kindergarten Children Collaboratively Retelling a "Kitsune" Story

ERIC Educational Resources Information Center

Oshiro, Aiko; Pihl, Agneta; Peterson, Louise; Pramling, Niklas

2017-01-01

How children understand the psychology of a story (i.e., the intentions and experiences of its characters) is pivotal to comprehending its point. In this study we investigate empirically how 5-year-old children in a Japanese kindergarten manage mental state verbs and adjectives when collaboratively retelling a tale heard. The tale, an example of a…

Artificial Reefs in Motion: Legacy of changes and degradation at the Redbird Reef Site

NASA Astrophysics Data System (ADS)

Trembanis, A. C.; DuVal, C.; Peter, B.

2016-12-01

Artificial reefs are used for a variety of purposes at sites throughout the U.S. and around the globe, yet little, if any, long-term monitoring has been conducted with the goal of understanding inter-annual changes to the emplaced structures. Throughout the U.S. Mid-Atlantic region, several programs utilized retired subway cars as disposal structures to form artificial reefs. One such site, known as site 11, or "Redbird Reef", is located off the coast of Delaware and was at one time home to 997 former NYC subway cars. Opportunistic sonar surveys at the site have been conducted between 2008 and 2016 providing one of the most extensive and repeated mapping studies for this type of reef. Previous studies conducted by our group at the site have focused on understanding wave orbital ripple dynamics and scour patterns. In this present study, we analyze the changes apparent at the site itself, focused on the storm-response dynamics of the subway cars. Results have shown that Superstorm Sandy in 2012 produced dramatic changes to the reef structures resulting in the total or partial destruction of eight subway cars within a small (.45 x .2km) portion of the reef site. Winter Storm Jonas in 2016 resulted in the destruction of fewer cars, but rotated a previously static 47m long Navy barge nearly 60 degrees. Once destroyed or collapsed by waves the subway cars go from providing positive structural relief and thus beneficial habitat above the surrounding seabed to being reduced to scattered low relief marine debris. A once popular consideration for reef material, the event and inter-annual decay of subway cars as observed at the Redbird reef provides both a stark indication of the power of storm dynamics on the inner-shelf and a cautionary tale with regards to the selection of seabed reef material.

Stellar Variability at the Main-sequence Turnoff of the Intermediate-age LMC Cluster NGC 1846

NASA Astrophysics Data System (ADS)

Salinas, R.; Pajkos, M. A.; Vivas, A. K.; Strader, J.; Contreras Ramos, R.

2018-04-01

Intermediate-age (IA) star clusters in the Large Magellanic Cloud (LMC) present extended main-sequence turn-offs (MSTO) that have been attributed to either multiple stellar populations or an effect of stellar rotation. Recently it has been proposed that these extended main sequences can also be produced by ill-characterized stellar variability. Here we present Gemini-S/Gemini Multi-Object Spectrometer (GMOS) time series observations of the IA cluster NGC 1846. Using differential image analysis, we identified 73 new variable stars, with 55 of those being of the Delta Scuti type, that is, pulsating variables close the MSTO for the cluster age. Considering completeness and background contamination effects, we estimate the number of δ Sct belonging to the cluster between 40 and 60 members, although this number is based on the detection of a single δ Sct within the cluster half-light radius. This amount of variable stars at the MSTO level will not produce significant broadening of the MSTO, albeit higher-resolution imaging will be needed to rule out variable stars as a major contributor to the extended MSTO phenomenon. Though modest, this amount of δ Sct makes NGC 1846 the star cluster with the highest number of these variables ever discovered. Lastly, our results present a cautionary tale about the adequacy of shallow variability surveys in the LMC (like OGLE) to derive properties of its δ Sct population. Based on observations obtained at the Gemini Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (United States), the National Research Council (Canada), CONICYT (Chile), Ministerio de Ciencia, Tecnología e Innovación Productiva (Argentina), and Ministério da Ciência, Tecnologia e Inovação (Brazil).

Targeting the Bacterial Cytoskeleton of the Burkholderia cepacia Complex for Antimicrobial Development: A Cautionary Tale.

PubMed

Carnell, Sonya C; Perry, John D; Borthwick, Lee; Vollmer, Daniela; Biboy, Jacob; Facchini, Marcella; Bragonzi, Alessandra; Silipo, Alba; Vergunst, Annette C; Vollmer, Waldemar; Khan, Anjam C M; De Soyza, Anthony

2018-05-30

Burkholderia cepacia complex (BCC) bacteria are a group of opportunistic pathogens that cause severe lung infections in cystic fibrosis (CF). Treatment of BCC infections is difficult, due to the inherent and acquired multidrug resistance of BCC. There is a pressing need to find new bacterial targets for antimicrobials. Here, we demonstrate that the novel compound Q22, which is related to the bacterial cytoskeleton destabilising compound A22, can reduce the growth rate and inhibit growth of BCC bacteria. We further analysed the phenotypic effects of Q22 treatment on BCC virulence traits, to assess its feasibility as an antimicrobial. BCC bacteria were grown in the presence of Q22 with a broad phenotypic analysis, including resistance to H₂O₂-induced oxidative stress, changes in the inflammatory potential of cell surface components, and in-vivo drug toxicity studies. The influence of the Q22 treatment on inflammatory potential was measured by monitoring the cytokine responses of BCC whole cell lysates, purified lipopolysaccharide, and purified peptidoglycan extracted from bacterial cultures grown in the presence or absence of Q22 in differentiated THP-1 cells. BCC bacteria grown in the presence of Q22 displayed varying levels of resistance to H₂O₂-induced oxidative stress, with some strains showing increased resistance after treatment. There was strain-to-strain variation in the pro-inflammatory ability of bacterial lysates to elicit TNFα and IL-1β from human myeloid cells. Despite minimal toxicity previously shown in vitro with primary CF cell lines, in-vivo studies demonstrated Q22 toxicity in both zebrafish and mouse infection models. In summary, destabilisation of the bacterial cytoskeleton in BCC, using compounds such as Q22, led to increased virulence-related traits in vitro. These changes appear to vary depending on strain and BCC species. Future development of antimicrobials targeting the BCC bacterial cytoskeleton may be hampered if such effects translate into the in-vivo environment of the CF infection.

The rise and fall of the lyme disease vaccines: a cautionary tale for risk interventions in American medicine and public health.

PubMed

Aronowitz, Robert A

2012-06-01

Two vaccines to prevent Lyme disease (LD) were developed and tested in the 1990s. Despite evidence of their safety and efficacy in clinical trials and initial postmarketing surveillance, one vaccine was withdrawn before the regulatory review and the other after only three years on the market. An investigation of their history can illuminate (1) the challenges faced by many new risk-reducing products and practices and (2) the important role played by their social and psychological, as distinct from their biomedical or scientific, efficacy in how they are used, and their ultimate market success or failure. This article reviewed medical and popular literature on LD vaccines, analyzed the regulatory hearings, and conducted interviews with key participants. Even if proved safe and effective, LD vaccines faced regulatory and market challenges because the disease was geographically limited, treatable, and preventable by other means. Pharmaceutical companies nevertheless hoped to appeal to consumers' desire for protection and control and to their widespread fear of the disease. The LD advocacy community initially supported the vaccines but soon became critical opponents. The vaccines' success was seen as threatening their central position that LD was chronic, protean, and difficult to treat. The activists' opposition flipped the vaccines' social and psychological efficacy. Instead of the vaccines restoring control and reducing fear, demand was undermined by beliefs that the vaccines caused an LD-like syndrome. The social and psychological efficacy of many risk-reducing practices and products, such as new "personalized vaccines," is to provide insurance and reduce fear. Yet the actions of self-interested actors can easily undermine this appeal. In addition to evaluating the scientific efficacy and safety of these practices and products, policymakers and others need to understand, anticipate, and perhaps shape the potential social and psychological work they might do. © 2012 Milbank Memorial Fund.

Unintended consequences of management actions in salt pond restoration: cascading effects in trophic interactions

USGS Publications Warehouse

Takekawa, John Y.; Ackerman, Joshua T.; Brand, Arriana; Graham, Tanya R.; Eagles-Smith, Collin A.; Herzog, Mark; Topping, Brent R.; Shellenbarger, Gregory; Kuwabara, James S.; Mruz, Eric; Piotter, Sara L.; Athearn, Nicole D.

2015-01-01

Salt evaporation ponds have played an important role as habitat for migratory waterbirds across the world, however, efforts to restore and manage these habitats to maximize their conservation value has proven to be challenging. For example, salinity reduction has been a goal for restoring and managing former salt evaporation ponds to support waterbirds in the South Bay Salt Pond Restoration Project in San Francisco Bay, California, USA. Here, we describe a case study of unexpected consequences of a low-dissolved oxygen (DO) event on trophic interactions in a salt pond system following management actions to reduce salinity concentrations. We document the ramifications of an anoxic event in water quality including salinity, DO, and temperature, and in the response of the biota including prey fish biomass, numerical response by California Gulls (Larus californicus), and chick survival of Forster's Tern (Sterna forsteri). Management actions intended to protect receiving waters resulted in decreased DO concentrations that collapsed to zero for ≥ 4 consecutive days, resulting in an extensive fish kill. DO depletion likely resulted from an algal bloom that arose following transition of the pond system from high to low salinity as respiration and decomposition outpaced photosynthetic production. We measured a ≥ 6-fold increase in biomass of fish dropped on the levee by foraging avian predators compared with weeks prior to and following the low-DO event. California Gulls rapidly responded to the availability of aerobically-stressed and vulnerable fish and increased in abundance by two orders of magnitude. Mark-recapture analysis of 254 Forster's Tern chicks indicated that their survival declined substantially following the increase in gull abundance. Thus, management actions to reduce salinity concentrations resulted in cascading effects in trophic interactions that serves as a cautionary tale illustrating the importance of understanding the interaction of water quality and trophic structure when managing restoration of salt ponds.

Four Cornerstones for Ensuring a Sustainable Workforce and Opportunity for the Next Generation of Geoscientists

NASA Astrophysics Data System (ADS)

Keane, C. M.; Houlton, H. R.

2012-04-01

The great demographic shift underway in many developed nations is impacting the geosciences extraordinarily hard. We examine the situation in the United States as an example of how there are four clear overarching issues to establishing a sustainable geosciences workforce: Carrying Capacity of the Educational Sector, the fundamentals of meeting future demand, the issue of graduate quality, and the emerging challenge of sustaining the capacity building of future geoscientist generations. The United States currently hosts about half of all geoscientists globally and is facing the imminent, and in the case of the Federal geosciences workforce, attrition of the Baby Boom generation geoscientists. This demographic shift is impacting all parts of the geosciences and when coupled by internal shifts in the geosciences on subdisciplinary thrusts, the match between the skill portfolio of new graduates is not necessarily well-aligned with the exiting skills of retirees. In particular, the US geosciences face the challenge of, based on current demand, attrition, and graduation rates of being short nearly 150,000 geoscientists by 2021. At the same time, the educational community is seeing the retirement of faculty that are leading into constrained ability to educate students in a number of topics, especially those in the resource industries. Given current funding trends and priorities, this phenomenon is likely to be in a feedback loop and will complicate the broad skill portfolio of the future geosciences. We also examine the issues of global migration and how it does not appear to be nearly as important to addressing the challenges as assumed by many. In addition, the prospective future geosciences majors appear to be of lesser quality than even 5 years ago based on test score, yet we will also present several broad strategies and cautionary tales that can help the US, and likely the global, geosciences community to ensure a stable and effective future and how this is actually opening new opportunities for the next generation of geoscientists.

Season and preterm birth in Norway: A cautionary tale.

PubMed

Weinberg, Clarice R; Shi, Min; DeRoo, Lisa A; Basso, Olga; Skjærven, Rolv

2015-06-01

Preterm birth is a common, costly and dangerous pregnancy complication. Seasonality of risk would suggest modifiable causes. We examine seasonal effects on preterm birth, using data from the Medical Birth Registry of Norway (2,321,652 births), and show that results based on births are misleading and a fetuses-at-risk approach is essential. In our harmonic-regression Cox proportional hazards model we consider fetal risk of birth between 22 and 37 completed weeks of gestation. We examine effects of both day of year of conception (for early effects) and day of ongoing gestation (for seasonal effects on labour onset) as modifiers of gestational-age-based risk. Naïve analysis of preterm rates across days of birth shows compelling evidence for seasonality (P < 10(-152)). However, the reconstructed numbers of conceptions also vary with season (P < 10(-307)), confounding results by inducing seasonal variation in the age distribution of the fetal population at risk. When we instead properly treat fetuses as the individuals at risk, restrict analysis to pregnancies with relatively accurate ultrasound-based assessment of gestational age (available since 1998) and adjust for socio-demographic factors and maternal smoking, we find modest effects of both time of year of conception and time of year at risk, with peaks for early preterm near early January and early July. Analyses of seasonal effects on preterm birth are demonstrably vulnerable to confounding by seasonality of conception, measurement error in conception dating, and socio-demographic factors. The seasonal variation based on fetuses reveals two peaks for early preterm, coinciding with New Year's Day and the early July beginning of Norway's summer break, and may simply reflect a holiday-related pattern of unintended conception. Published by Oxford University Press on behalf of the International Epidemiological Association 2015. This work is written by a US Government employee and is in the public domain in the US.

National Administrative Databases in Adult Spinal Deformity Surgery: A Cautionary Tale.

PubMed

Buckland, Aaron J; Poorman, Gregory; Freitag, Robert; Jalai, Cyrus; Klineberg, Eric O; Kelly, Michael; Passias, Peter G

2017-08-15

Comparison between national administrative databases and a prospective multicenter physician managed database. This study aims to assess the applicability of National Administrative Databases (NADs) in adult spinal deformity (ASD). Our hypothesis is that NADs do not include comparable patients as in a physician-managed database (PMD) for surgical outcomes in adult spinal deformity. NADs such as National Inpatient Sample (NIS) and National Surgical Quality Improvement Program (NSQIP) provide large numbers of publications owing to ease of data access and lack of IRB approval requirement. These databases utilize billing codes, not clinical inclusion criteria, and have not been validated against PMDs in ASD surgery. The NIS was searched for years 2002 to 2012 and NSQIP for years 2006 to 2013 using validated spinal deformity diagnostic codes. Procedural codes (ICD-9 and CPT) were then applied to each database. A multicenter PMD including years 2008 to 2015 was used for comparison. Databases were assessed for levels fused, osteotomies, decompressed levels, and invasiveness. Database comparisons for surgical details were made in all patients, and also for patients with ≥ 5 level spinal fusions. Approximately, 37,368 NIS, 1291 NSQIP, and 737 PMD patients were identified. NADs showed an increased use of deformity billing codes over the study period (NIS doubled, 68x NSQIP, P < 0.001), but ASD remained stable in the PMD.Surgical invasiveness, levels fused and use of 3-column osteotomy (3-CO) were significantly lower for all patients in the NIS (11.4-13.7) and NSQIP databases (6.4-12.7) compared with PMD (27.5-32.3). When limited to patients with ≥5 levels, invasiveness, levels fused, and use of 3-CO remained significantly higher in the PMD compared with NADs (P < 0.001). National databases NIS and NSQIP do not capture the same patient population as is captured in PMDs in ASD. Physicians should remain cautious in interpreting conclusions drawn from these databases. 4.

Perils of police action: a cautionary tale from US data sets.

PubMed

Miller, Ted R; Lawrence, Bruce A; Carlson, Nancy N; Hendrie, Delia; Randall, Sean; Rockett, Ian R H; Spicer, Rebecca S

2017-02-01

To count and characterise injuries resulting from legal intervention by US law enforcement personnel and injury ratios per 10 000 arrests or police stops, thus expanding discussion of excessive force by police beyond fatalities. Ecological. Those injured during US legal police intervention as recorded in 2012 Vital Statistics mortality census, 2012 Healthcare Cost and Utilization Project nationwide inpatient and emergency department samples, and two 2015 newspaper censuses of deaths. 2012 and 2014 arrests from Federal Bureau of Investigation data adjusted for non-reporting jurisdictions; street stops and traffic stops that involved vehicle or occupant searches, without arrest, from the 2011 Police Public Contact Survey (PPCS), with the percentage breakdown by race computed from pooled 2005, 2008 and 2011 PPCS surveys due to small case counts. US police killed or injured an estimated 55 400 people in 2012 (95% CI 47 050 to 63 740 for cases coded as police involved). Blacks, Native Americans and Hispanics had higher stop/arrest rates per 10 000 population than white non-Hispanics and Asians. On average, an estimated 1 in 291 stops/arrests resulted in hospital-treated injury or death of a suspect or bystander. Ratios of admitted and fatal injury due to legal police intervention per 10 000 stops/arrests did not differ significantly between racial/ethnic groups. Ratios rose with age, and were higher for men than women. Healthcare administrative data sets can inform public debate about injuries resulting from legal police intervention. Excess per capita death rates among blacks and youth at police hands are reflections of excess exposure. International Classification of Diseases legal intervention coding needs revision. 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/.

Bayesian investigation of isochrone consistency using the old open cluster NGC 188

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

Hills, Shane; Courteau, Stéphane; Von Hippel, Ted

2015-03-01

This paper provides a detailed comparison of the differences in parameters derived for a star cluster from its color–magnitude diagrams (CMDs) depending on the filters and models used. We examine the consistency and reliability of fitting three widely used stellar evolution models to 15 combinations of optical and near-IR photometry for the old open cluster NGC 188. The optical filter response curves match those of theoretical systems and are thus not the source of fit inconsistencies. NGC 188 is ideally suited to this study thanks to a wide variety of high-quality photometry and available proper motions and radial velocities thatmore » enable us to remove non-cluster members and many binaries. Our Bayesian fitting technique yields inferred values of age, metallicity, distance modulus, and absorption as a function of the photometric band combinations and stellar models. We show that the historically favored three-band combinations of UBV and VRI can be meaningfully inconsistent with each other and with longer baseline data sets such as UBVRIJHK{sub S}. Differences among model sets can also be substantial. For instance, fitting Yi et al. (2001) and Dotter et al. (2008) models to UBVRIJHK{sub S} photometry for NGC 188 yields the following cluster parameters: age = (5.78 ± 0.03, 6.45 ± 0.04) Gyr, [Fe/H] = (+0.125 ± 0.003, −0.077 ± 0.003) dex, (m−M){sub V} = (11.441 ± 0.007, 11.525 ± 0.005) mag, and A{sub V} = (0.162 ± 0.003, 0.236 ± 0.003) mag, respectively. Within the formal fitting errors, these two fits are substantially and statistically different. Such differences among fits using different filters and models are a cautionary tale regarding our current ability to fit star cluster CMDs. Additional modeling of this kind, with more models and star clusters, and future Gaia parallaxes are critical for isolating and quantifying the most relevant uncertainties in stellar evolutionary models.« less

Net Ecosystem Production and Actionable Negative Emissions Strategies

NASA Astrophysics Data System (ADS)

DeCicco, J. M.; Heo, J.

2016-12-01

Negative emissions strategies, designed to increase the rate at which carbon dioxide (CO2) and other greenhouse gases are removed from the atmosphere, are an important aspect of broader strategies for mitigating climate change. Not only is CO2 the dominant greenhouse gas and the one most intimately tied to existing commercial energy use, but it is also part of the global carbon cycle. On the order of 200 PgC•yr-1 circulates between the atmosphere and the major carbon stocks of the terrestrial biosphere, oceans and geosphere. Anthropogenic flows of roughly 10 PgC•yr-1 from fossil fuel use and 1 PgC•yr-1 from land-use change significantly exceed the Earth's natural carbon sink, and this imbalance causes the buildup of carbon in the atmosphere. In addition to strategies for reducing CO2 emissions, increasing negative emissions through carbon dioxide removal (CDR) is crucial for reducing carbon cycle imbalance in the near term as well as meeting long-term goals such as a 2°C limit. Terrestrial carbon management is important for both reducing emissions and enhancing sinks. Photosynthesis in terrestrial ecosystems is the form of CDR that is now most actionable, referring to mechanisms that can be economically implemented at meaningful scales without technology breakthroughs. Net ecosystem production (NEP) is a crucial metric for guiding CDR involving the terrestrial biosphere, including options such as bioenergy with carbon capture and storage (BECCS) and other forms of bio-based mitigation. We derive the necessary conditions for effective implementation of this category of negative emissions measures, emphasizing the importance of NEP measurement, baselines and appropriate methods of carbon accounting. We present a method for quantitative spatio-temporal analysis of land-use and land-cover changes for estimating landscape-scale NEP; provide a preliminary baseline NEP estimate for the continental United States; apply the method to reveal a cautionary tale regarding NEP and biofuel production; and discuss the implications for negative emissions research and public policy going forward.

Two transitional type Ia supernovae located in the Fornax cluster member NGC 1404: SN 2007on and SN 2011iv

NASA Astrophysics Data System (ADS)

Gall, C.; Stritzinger, M. D.; Ashall, C.; Baron, E.; Burns, C. R.; Hoeflich, P.; Hsiao, E. Y.; Mazzali, P. A.; Phillips, M. M.; Filippenko, A. V.; Anderson, J. P.; Benetti, S.; Brown, P. J.; Campillay, A.; Challis, P.; Contreras, C.; Elias de la Rosa, N.; Folatelli, G.; Foley, R. J.; Fraser, M.; Holmbo, S.; Marion, G. H.; Morrell, N.; Pan, Y.-C.; Pignata, G.; Suntzeff, N. B.; Taddia, F.; Robledo, S. Torres; Valenti, S.

2018-03-01

We present an analysis of ultraviolet (UV) to near-infrared observations of the fast-declining Type Ia supernovae (SNe Ia) 2007on and 2011iv, hosted by the Fornax cluster member NGC 1404. The B-band light curves of SN 2007on and SN 2011iv are characterised by Δm15 (B) decline-rate values of 1.96 mag and 1.77 mag, respectively. Although they have similar decline rates, their peak B- and H-band magnitudes differ by 0.60 mag and 0.35 mag, respectively. After correcting for the luminosity vs. decline rate and the luminosity vs. colour relations, the peak B-band and H-band light curves provide distances that differ by 14% and 9%, respectively. These findings serve as a cautionary tale for the use of transitional SNe Ia located in early-type hosts in the quest to measure cosmological parameters. Interestingly, even though SN 2011iv is brighter and bluer at early times, by three weeks past maximum and extending over several months, its B - V colour is 0.12 mag redder than that of SN 2007on. To reconcile this unusual behaviour, we turn to guidance from a suite of spherical one-dimensional Chandrasekhar-mass delayed-detonation explosion models. In this context, 56Ni production depends on both the so-called transition density and the central density of the progenitor white dwarf. To first order, the transition density drives the luminosity-width relation, while the central density is an important second-order parameter. Within this context, the differences in the B - V colour evolution along the Lira regime suggest that the progenitor of SN 2011iv had a higher central density than SN 2007on. The photometry tables are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/611/A58

Commentary: A cautionary tale regarding use of the National Land Cover Dataset 1992

USGS Publications Warehouse

Thogmartin, Wayne E.; Gallant, Alisa L.; Knutson, Melinda G.; Fox, Timothy J.; Suarez, Manuel J.

2004-01-01

Digital land-cover data are among the most popular data sources used in ecological research and natural resource management. However, processes for accurate land-cover classification over large regions are still evolving. We identified inconsistencies in the National Land Cover Dataset 1992, the most current and available representation of land cover for the conterminous United States. We also report means to address these inconsistencies in a bird-habitat model. We used a Geographic Information System (GIS) to position a regular grid (or lattice) over the upper midwestern United States and summarized the proportion of individual land covers in each cell within the lattice. These proportions were then mapped back onto the lattice, and the resultant lattice was compared to satellite paths, state borders, and regional map classification units. We observed mapping inconsistencies at the borders between mapping regions, states, and Thematic Mapper (TM) mapping paths in the upper midwestern United States, particularly related to grass I and-herbaceous, emergent-herbaceous wetland, and small-grain land covers. We attributed these discrepancies to differences in image dates between mapping regions, suboptimal image dates for distinguishing certain land-cover types, lack of suitable ancillary data for improving discrimination for rare land covers, and possibly differences among image interpreters. To overcome these inconsistencies for the purpose of modeling regional populations of birds, we combined grassland-herbaceous and pasture-hay land-cover classes and excluded the use of emergent-herbaceous and small-grain land covers. We recommend that users of digital land-cover data conduct similar assessments for other regions before using these data for habitat evaluation. Further, caution is advised in using these data in the analysis of regional land-cover change because it is not likely that future digital land-cover maps will repeat the same problems, thus resulting in biased estimates of change.

Knowledge, attitudes, and practices toward malaria risk and prevention among frequent business travelers of a major oil and gas company.

PubMed

Berg, Johannes; Breederveld, Daan; Roukens, Anna H; Hennink, Yvonne; Schouten, Marjolijn; Wendt, Judy K; Visser, Leo G

2011-01-01

Despite significant morbidity and mortality among business travelers due to malaria, very little has been published on knowledge, attitudes, and practices (KAP) toward malaria risk. The aim of this study was to assess KAP among frequent international business travelers (FBT) and to identify recommendations for improving malaria prevention that could be applied to the wider FBT community in occupational health. A retrospective web-based survey was conducted in 2005 among self-registered FBT of an oil and gas company based in the Netherlands. The survey was completed by 328 of the 608 self-registered FBT (54%). Fifty-four percent of respondents had visited a high-risk area for malaria. Most respondents (96%) were experienced travelers; the majority (71%) sought health advice before their trip and made use of a company health resource. Fever was recognized as a malaria symptom by all FBT; travel to high-risk malaria areas was correctly identified by 96%, and 99% of these travelers adhered to use of adequate personal protective measures. The proportion of travelers carrying appropriate anti-malaria drug regimen was positively associated with receiving company advice among FBT traveling to high-risk destinations (RR = 2.10, 95% CI: 1.21-3.67), but not for those traveling to low- or no-risk destinations. Only 8% (14) of those going to a high-risk area were not carrying malaria prophylaxis. One in five of FBT traveling to no-risk areas were unnecessarily carrying malaria prophylaxis. The majority of KAP results were excellent. We postulate that a company culture with a strong focus on health, safety, security, and environment can positively contribute to high KAP scores. Notwithstanding the excellent findings, this study also provides a cautionary tale for company health functions against overprescribing of malaria prophylaxis. It demonstrates the need for constant review and audit of adherence to quality criteria. © 2011 International Society of Travel Medicine.

The adenoid: Its history and a cautionary tale.

PubMed

Ruben, Robert J

2017-06-01

The existence of the adenoid first appears to have been noted by Conrad Victor Schneider in 1661. James Yearsley reported in 1842 one case in which he improved hearing by removal of a mucus membrane from behind the uvula, which indicates some appreciation of a relationship of the nasopharynx to ear disease. Hans Wilhelm Meyer, in 1868, was the first to demonstrate the relationship of the adenoid to ear disease and to develop an effective, although somewhat difficult, surgical operation to remove the adenoid. Removal of the adenoid became rapidly accepted worldwide as a treatment for many morbidities, including otitis, speech problems, cognitive problems, and sleep apnea. Until the 1920s, adenoidectomy often was performed as a staged procedure and without general anesthesia. Early tools and techniques included use of the bare fingernail, a finger ring knife, a curette, and electrical desiccation. From the mid-1930s to the early 1960s, radiation therapy of the adenoid was in extensive use, both for children and in caring for army aviators and navy submarine crews during WWII. The effectiveness of surgical adenoidectomy for hearing loss led to a belief that radiation, which had been found to ablate lymphoid tissue, would be equally effective, and led to the wide-spread use of radiation. Ultimately, 500 thousand to 2.5 million children and adults were estimated to have been treated with radiation, and follow-up studies found increased risk for cancer. Furthermore, a follow-up study by Stacey R. Guild (1890-1966), published in 1950, on a very large sample of children who previously were reported to have had their hearing loss diminished through radiation, found that irradiation had produced no effect on high-tone loss. Thus, irradiation was both useless and harmful. Acceptance of authority, which can lurk within medical culture, led to the development of a tragically misguided management of adenoid disease. Laryngoscope, 127:S13-S28, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Unintended Consequences of Management Actions in Salt Pond Restoration: Cascading Effects in Trophic Interactions

PubMed Central

Takekawa, John Y.; Ackerman, Joshua T.; Brand, L. Arriana; Graham, Tanya R.; Eagles-Smith, Collin A.; Herzog, Mark P.; Topping, Brent R.; Shellenbarger, Gregory G.; Kuwabara, James S.; Mruz, Eric; Piotter, Sara L.; Athearn, Nicole D.

2015-01-01

Salt evaporation ponds have played an important role as habitat for migratory waterbirds across the world, however, efforts to restore and manage these habitats to maximize their conservation value has proven to be challenging. For example, salinity reduction has been a goal for restoring and managing former salt evaporation ponds to support waterbirds in the South Bay Salt Pond Restoration Project in San Francisco Bay, California, USA. Here, we describe a case study of unexpected consequences of a low-dissolved oxygen (DO) event on trophic interactions in a salt pond system following management actions to reduce salinity concentrations. We document the ramifications of an anoxic event in water quality including salinity, DO, and temperature, and in the response of the biota including prey fish biomass, numerical response by California Gulls (Larus californicus), and chick survival of Forster's Tern (Sterna forsteri). Management actions intended to protect receiving waters resulted in decreased DO concentrations that collapsed to zero for ≥ 4 consecutive days, resulting in an extensive fish kill. DO depletion likely resulted from an algal bloom that arose following transition of the pond system from high to low salinity as respiration and decomposition outpaced photosynthetic production. We measured a ≥ 6-fold increase in biomass of fish dropped on the levee by foraging avian predators compared with weeks prior to and following the low-DO event. California Gulls rapidly responded to the availability of aerobically-stressed and vulnerable fish and increased in abundance by two orders of magnitude. Mark-recapture analysis of 254 Forster's Tern chicks indicated that their survival declined substantially following the increase in gull abundance. Thus, management actions to reduce salinity concentrations resulted in cascading effects in trophic interactions that serves as a cautionary tale illustrating the importance of understanding the interaction of water quality and trophic structure when managing restoration of salt ponds. PMID:26030415

Rescaling quality of life values from discrete choice experiments for use as QALYs: a cautionary tale

PubMed Central

Flynn, Terry N; Louviere, Jordan J; Marley, Anthony AJ; Coast, Joanna; Peters, Tim J

2008-01-01

Background Researchers are increasingly investigating the potential for ordinal tasks such as ranking and discrete choice experiments to estimate QALY health state values. However, the assumptions of random utility theory, which underpin the statistical models used to provide these estimates, have received insufficient attention. In particular, the assumptions made about the decisions between living states and the death state are not satisfied, at least for some people. Estimated values are likely to be incorrectly anchored with respect to death (zero) in such circumstances. Methods Data from the Investigating Choice Experiments for the preferences of older people CAPability instrument (ICECAP) valuation exercise were analysed. The values (previously anchored to the worst possible state) were rescaled using an ordinal model proposed previously to estimate QALY-like values. Bootstrapping was conducted to vary artificially the proportion of people who conformed to the conventional random utility model underpinning the analyses. Results Only 26% of respondents conformed unequivocally to the assumptions of conventional random utility theory. At least 14% of respondents unequivocally violated the assumptions. Varying the relative proportions of conforming respondents in sensitivity analyses led to large changes in the estimated QALY values, particularly for lower-valued states. As a result these values could be either positive (considered to be better than death) or negative (considered to be worse than death). Conclusion Use of a statistical model such as conditional (multinomial) regression to anchor quality of life values from ordinal data to death is inappropriate in the presence of respondents who do not conform to the assumptions of conventional random utility theory. This is clearest when estimating values for that group of respondents observed in valuation samples who refuse to consider any living state to be worse than death: in such circumstances the model cannot be estimated. Only a valuation task requiring respondents to make choices in which both length and quality of life vary can produce estimates that properly reflect the preferences of all respondents. PMID:18945358

Studying Resistance: Some Cautionary Notes

ERIC Educational Resources Information Center

Dimitriadis, Greg

2011-01-01

The question of "resistance" has oriented the field of critical ethnography for several generations now. Indeed, the reproduction-resistance binary has animated much of the most important, critical work in educational studies over the last 30 years. Yet, this reproduction-resistance binary has perhaps calcified in recent years. Such work…

Media Matters

ERIC Educational Resources Information Center

Cooper, Kenneth J.; Pyrillis, Rita; Rosario, Ruben; Stuart, Reginald; Zinngrabe, Elaine

2007-01-01

This article presents five vignettes, written by veteran journalists, that focus on the current and future state of journalism. Despite almost daily reports of media consolidation and newspaper layoffs, the journalists sound a cautionary but optimistic tone about the industry. They weigh in on everything from the threats to diversity to the future…

The fairy tale as paradigm of the separation-individuation crisis: implications for treatment of the borderline adolescent.

PubMed

Brandt, L M

1983-01-01

This chapter is an attempt to offer a model for therapeutic work with borderline patients that is based on the structure and content of the fairy tale. It views the fairy tale as both descriptive in its echoing of developmental struggles of childhood and integrative in providing a model for resolution of these conflicts. Clare's use of the fairy tale offers confirmation of theoretical notions which place the etiology of borderline pathology in early developmental failures and a clue to the therapeutic work with borderline patients. While the childhood route of the fairy tale may no longer be available to most, its subtle mirroring of the separation-individuation crisis and gradual, growthful steps toward integration of both the external and the internal worlds offer an exquisite model for the work of psychotherapy. "Once a king in Narnia , always a king in Narnia . But don't go trying to use the same route twice. . ." (Lewis 1950, p. 186).

Visualization of aging-associated chromatin alterations with an engineered TALE system

PubMed Central

Ren, Ruotong; Deng, Liping; Xue, Yanhong; Suzuki, Keiichiro; Zhang, Weiqi; Yu, Yang; Wu, Jun; Sun, Liang; Gong, Xiaojun; Luan, Huiqin; Yang, Fan; Ju, Zhenyu; Ren, Xiaoqing; Wang, Si; Tang, Hong; Geng, Lingling; Zhang, Weizhou; Li, Jian; Qiao, Jie; Xu, Tao; Qu, Jing; Liu, Guang-Hui

2017-01-01

Visualization of specific genomic loci in live cells is a prerequisite for the investigation of dynamic changes in chromatin architecture during diverse biological processes, such as cellular aging. However, current precision genomic imaging methods are hampered by the lack of fluorescent probes with high specificity and signal-to-noise contrast. We find that conventional transcription activator-like effectors (TALEs) tend to form protein aggregates, thereby compromising their performance in imaging applications. Through screening, we found that fusing thioredoxin with TALEs prevented aggregate formation, unlocking the full power of TALE-based genomic imaging. Using thioredoxin-fused TALEs (TTALEs), we achieved high-quality imaging at various genomic loci and observed aging-associated (epi) genomic alterations at telomeres and centromeres in human and mouse premature aging models. Importantly, we identified attrition of ribosomal DNA repeats as a molecular marker for human aging. Our study establishes a simple and robust imaging method for precisely monitoring chromatin dynamics in vitro and in vivo. PMID:28139645

Benchmarking of TALE- and CRISPR/dCas9-Based Transcriptional Regulators in Mammalian Cells for the Construction of Synthetic Genetic Circuits.

PubMed

Lebar, Tina; Jerala, Roman

2016-10-21

Transcriptional activator-like effector (TALE)- and CRISPR/Cas9-based designable recognition domains represent a technological breakthrough not only for genome editing but also for building designed genetic circuits. Both platforms are able to target rarely occurring DNA segments, even within complex genomes. TALE and dCas9 domains, genetically fused to transcriptional regulatory domains, can be used for the construction of engineered logic circuits. Here we benchmarked the performance of the two platforms, targeting the same DNA sequences, to compare their advantages for the construction of designed circuits in mammalian cells. Optimal targeting strands for repression and activation of dCas9-based designed transcription factors were identified; both platforms exhibited good orthogonality and were used to construct functionally complete NOR gates. Although the CRISPR/dCas9 system is clearly easier to construct, TALE-based activators were significantly stronger, and the TALE-based platform performed better, especially for the construction of layered circuits.

Molecular insights into the origin of the Hox-TALE patterning system

PubMed Central

Hudry, Bruno; Thomas-Chollier, Morgane; Volovik, Yael; Duffraisse, Marilyne; Dard, Amélie; Frank, Dale; Technau, Ulrich; Merabet, Samir

2014-01-01

Despite tremendous body form diversity in nature, bilaterian animals share common sets of developmental genes that display conserved expression patterns in the embryo. Among them are the Hox genes, which define different identities along the anterior–posterior axis. Hox proteins exert their function by interaction with TALE transcription factors. Hox and TALE members are also present in some but not all non-bilaterian phyla, raising the question of how Hox–TALE interactions evolved to provide positional information. By using proteins from unicellular and multicellular lineages, we showed that these networks emerged from an ancestral generic motif present in Hox and other related protein families. Interestingly, Hox-TALE networks experienced additional and extensive molecular innovations that were likely crucial for differentiating Hox functions along body plans. Together our results highlight how homeobox gene families evolved during eukaryote evolution to eventually constitute a major patterning system in Eumetazoans. DOI: http://dx.doi.org/10.7554/eLife.01939.001 PMID:24642410

Molecular insights into the origin of the Hox-TALE patterning system.

PubMed

Hudry, Bruno; Thomas-Chollier, Morgane; Volovik, Yael; Duffraisse, Marilyne; Dard, Amélie; Frank, Dale; Technau, Ulrich; Merabet, Samir

2014-03-18

Despite tremendous body form diversity in nature, bilaterian animals share common sets of developmental genes that display conserved expression patterns in the embryo. Among them are the Hox genes, which define different identities along the anterior-posterior axis. Hox proteins exert their function by interaction with TALE transcription factors. Hox and TALE members are also present in some but not all non-bilaterian phyla, raising the question of how Hox-TALE interactions evolved to provide positional information. By using proteins from unicellular and multicellular lineages, we showed that these networks emerged from an ancestral generic motif present in Hox and other related protein families. Interestingly, Hox-TALE networks experienced additional and extensive molecular innovations that were likely crucial for differentiating Hox functions along body plans. Together our results highlight how homeobox gene families evolved during eukaryote evolution to eventually constitute a major patterning system in Eumetazoans. DOI: http://dx.doi.org/10.7554/eLife.01939.001.

Spatial organization of heterologous metabolic system in vivo based on TALE.

PubMed

Zhu, Lv-yun; Qiu, Xin-Yuan; Zhu, Ling-Yun; Wu, Xiao-Min; Zhang, Yuan; Zhu, Qian-Hui; Fan, Dong-Yu; Zhu, Chu-Shu; Zhang, Dong-Yi

2016-05-17

For years, prokaryotic hosts have been widely applied in bio-engineering. However, the confined in vivo enzyme clustering of heterologous metabolic pathways in these organisms often results in low local concentrations of enzymes and substrates, leading to a low productive efficacy. We developed a new method to accelerate a heterologous metabolic system by integrating a transcription activator-like effector (TALE)-based scaffold system into an Escherichia coli chassis. The binding abilities of the TALEs to the artificial DNA scaffold were measured through ChIP-PCR. The effect of the system was determined through a split GFP study and validated through the heterologous production of indole-3-acetic acid (IAA) by incorporating TALE-fused IAA biosynthetic enzymes in E. coli. To the best of our knowledge, we are the first to use the TALE system as a scaffold for the spatial organization of bacterial metabolism. This technique might be used to establish multi-enzymatic reaction programs in a prokaryotic chassis for various applications.

Interrogating Key Positions of Size-Reduced TALE Repeats Reveals a Programmable Sensor of 5-Carboxylcytosine.

PubMed

Maurer, Sara; Giess, Mario; Koch, Oliver; Summerer, Daniel

2016-12-16

Transcription-activator-like effector (TALE) proteins consist of concatenated repeats that recognize consecutive canonical nucleobases of DNA via the major groove in a programmable fashion. Since this groove displays unique chemical information for the four human epigenetic cytosine nucleobases, TALE repeats with epigenetic selectivity can be engineered, with potential to establish receptors for the programmable decoding of all human nucleobases. TALE repeats recognize nucleobases via key amino acids in a structurally conserved loop whose backbone is positioned very close to the cytosine 5-carbon. This complicates the engineering of selectivities for large 5-substituents. To interrogate a more promising structural space, we engineered size-reduced repeat loops, performed saturation mutagenesis of key positions, and screened a total of 200 repeat-nucleobase interactions for new selectivities. This provided insight into the structural requirements of TALE repeats for affinity and selectivity, revealed repeats with improved or relaxed selectivity, and resulted in the first selective sensor of 5-carboxylcytosine.

From Tales of the Tongue to Tales of the Pen: An Organic Approach to Children's Literature. Resource Guide. NEH 1989 Summer Institute.

ERIC Educational Resources Information Center

Southwest Texas State Univ., San Marcos. Dept. of English.

Developed from the activities of a summer institute in Texas that focused on "The Odyssey," folk and fairy tale, and folk rhyme, this resource guide presents 50 lesson plans offering a variety of approaches to teaching mythology and folklore to elementary school students. The lesson plans presented in the resource guide share a common…

TALE-mediated epigenetic suppression of CDKN2A increases replication in human fibroblasts.

PubMed

Bernstein, Diana L; Le Lay, John E; Ruano, Elena G; Kaestner, Klaus H

2015-05-01

Current strategies to alter disease-associated epigenetic modifications target ubiquitously expressed epigenetic regulators. This approach does not allow specific genes to be controlled in specific cell types; therefore, tools to selectively target epigenetic modifications in the desired cell type and strategies to more efficiently correct aberrant gene expression in disease are needed. Here, we have developed a method for directing DNA methylation to specific gene loci by conjugating catalytic domains of DNA methyltransferases (DNMTs) to engineered transcription activator-like effectors (TALEs). We demonstrated that these TALE-DNMTs direct DNA methylation specifically to the targeted gene locus in human cells. Further, we determined that minimizing direct nucleotide sequence repeats within the TALE moiety permits efficient lentivirus transduction, allowing easy targeting of primary cell types. Finally, we demonstrated that directed DNA methylation with a TALE-DNMT targeting the CDKN2A locus, which encodes the cyclin-dependent kinase inhibitor p16, decreased CDKN2A expression and increased replication of primary human fibroblasts, as intended. Moreover, overexpression of p16 in these cells reversed the proliferative phenotype, demonstrating the specificity of our epigenetic targeting. Together, our results demonstrate that TALE-DNMTs can selectively target specific genes and suggest that this strategy has potential application for the development of locus-specific epigenetic therapeutics.

Engineering synthetic TAL effectors with orthogonal target sites

PubMed Central

Garg, Abhishek; Lohmueller, Jason J.; Silver, Pamela A.; Armel, Thomas Z.

2012-01-01

The ability to engineer biological circuits that process and respond to complex cellular signals has the potential to impact many areas of biology and medicine. Transcriptional activator-like effectors (TALEs) have emerged as an attractive component for engineering these circuits, as TALEs can be designed de novo to target a given DNA sequence. Currently, however, the use of TALEs is limited by degeneracy in the site-specific manner by which they recognize DNA. Here, we propose an algorithm to computationally address this problem. We apply our algorithm to design 180 TALEs targeting 20 bp cognate binding sites that are at least 3 nt mismatches away from all 20 bp sequences in putative 2 kb human promoter regions. We generated eight of these synthetic TALE activators and showed that each is able to activate transcription from a targeted reporter. Importantly, we show that these proteins do not activate synthetic reporters containing mismatches similar to those present in the genome nor a set of endogenous genes predicted to be the most likely targets in vivo. Finally, we generated and characterized TALE repressors comprised of our orthogonal DNA binding domains and further combined them with shRNAs to accomplish near complete repression of target gene expression. PMID:22581776

TALE-mediated epigenetic suppression of CDKN2A increases replication in human fibroblasts

PubMed Central

Bernstein, Diana L.; Le Lay, John E.; Ruano, Elena G.; Kaestner, Klaus H.

2015-01-01

Current strategies to alter disease-associated epigenetic modifications target ubiquitously expressed epigenetic regulators. This approach does not allow specific genes to be controlled in specific cell types; therefore, tools to selectively target epigenetic modifications in the desired cell type and strategies to more efficiently correct aberrant gene expression in disease are needed. Here, we have developed a method for directing DNA methylation to specific gene loci by conjugating catalytic domains of DNA methyltransferases (DNMTs) to engineered transcription activator–like effectors (TALEs). We demonstrated that these TALE-DNMTs direct DNA methylation specifically to the targeted gene locus in human cells. Further, we determined that minimizing direct nucleotide sequence repeats within the TALE moiety permits efficient lentivirus transduction, allowing easy targeting of primary cell types. Finally, we demonstrated that directed DNA methylation with a TALE-DNMT targeting the CDKN2A locus, which encodes the cyclin-dependent kinase inhibitor p16, decreased CDKN2A expression and increased replication of primary human fibroblasts, as intended. Moreover, overexpression of p16 in these cells reversed the proliferative phenotype, demonstrating the specificity of our epigenetic targeting. Together, our results demonstrate that TALE-DNMTs can selectively target specific genes and suggest that this strategy has potential application for the development of locus-specific epigenetic therapeutics. PMID:25866970

TALEs from a spring--superelasticity of Tal effector protein structures.

PubMed

Flechsig, Holger

2014-01-01

Transcription activator-like effectors (TALEs) are DNA-related proteins that recognise and bind specific target sequences to manipulate gene expression. Recently determined crystal structures show that their common architecture reveals a superhelical overall structure that may undergo drastic conformational changes. To establish a link between structure and dynamics in TALE proteins we have employed coarse-grained elastic-network modelling of currently available structural data and implemented a force-probe setup that allowed us to investigate their mechanical behaviour in computer experiments. Based on the measured force-extension curves we conclude that TALEs exhibit superelastic dynamical properties allowing for large-scale global conformational changes along their helical axis, which represents the soft direction in such proteins. For moderate external forcing the TALE models behave like linear springs, obeying Hooke's law, and the investigated structures can be characterised and compared by a corresponding spring constant. We show that conformational flexibility underlying the large-scale motions is not homogeneously distributed over the TALE structure, but instead soft spot residues around which strain is accumulated and which turn out to represent key agents in the transmission of conformational motions are identified. They correspond to the RVD loop residues that have been experimentally determined to play an eminent role in the binding process of target DNA.

TALEs from a Spring – Superelasticity of Tal Effector Protein Structures

PubMed Central

Flechsig, Holger

2014-01-01

Transcription activator-like effectors (TALEs) are DNA-related proteins that recognise and bind specific target sequences to manipulate gene expression. Recently determined crystal structures show that their common architecture reveals a superhelical overall structure that may undergo drastic conformational changes. To establish a link between structure and dynamics in TALE proteins we have employed coarse-grained elastic-network modelling of currently available structural data and implemented a force-probe setup that allowed us to investigate their mechanical behaviour in computer experiments. Based on the measured force-extension curves we conclude that TALEs exhibit superelastic dynamical properties allowing for large-scale global conformational changes along their helical axis, which represents the soft direction in such proteins. For moderate external forcing the TALE models behave like linear springs, obeying Hooke's law, and the investigated structures can be characterised and compared by a corresponding spring constant. We show that conformational flexibility underlying the large-scale motions is not homogeneously distributed over the TALE structure, but instead soft spot residues around which strain is accumulated and which turn out to represent key agents in the transmission of conformational motions are identified. They correspond to the RVD loop residues that have been experimentally determined to play an eminent role in the binding process of target DNA. PMID:25313859

Targeted repression of AXIN2 and MYC gene expression using designer TALEs

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

Rennoll, Sherri A.; Scott, Samantha A.; Yochum, Gregory S., E-mail: gsy3@psu.edu

Highlights: • We designed TALE–SID fusion proteins to target AXIN2 and MYC. • TALE–SIDs bound the chromosomal AXIN2 and MYC genes and repressed their expression. • TALE–SIDs repress β-catenin{sup S45F}-dependent AXIN2 and MYC transcription. - Abstract: Designer TALEs (dTALEs) are chimeric transcription factors that can be engineered to regulate gene expression in mammalian cells. Whether dTALEs can block gene transcription downstream of signal transduction cascades, however, has yet to be fully explored. Here we tested whether dTALEs can be used to target genes whose expression is controlled by Wnt/β-catenin signaling. TALE DNA binding domains were engineered to recognize sequences adjacentmore » to Wnt responsive enhancer elements (WREs) that control expression of axis inhibition protein 2 (AXIN2) and c-MYC (MYC). These custom DNA binding domains were linked to the mSin3A interaction domain (SID) to generate TALE–SID chimeric repressors. The TALE–SIDs repressed luciferase reporter activity, bound their genomic target sites, and repressed AXIN2 and MYC expression in HEK293 cells. We generated a novel HEK293 cell line to determine whether the TALE–SIDs could function downstream of oncogenic Wnt/β-catenin signaling. Treating these cells with doxycycline and tamoxifen stimulates nuclear accumulation of a stabilized form of β-catenin found in a subset of colorectal cancers. The TALE–SIDs repressed AXIN2 and MYC expression in these cells, which suggests that dTALEs could offer an effective therapeutic strategy for the treatment of colorectal cancer.« less

Regulation of CCL2 expression by an upstream TALE homeodomain protein-binding site that synergizes with the site created by the A-2578G SNP.

PubMed

Page, Stephen H; Wright, Edward K; Gama, Lucio; Clements, Janice E

2011-01-01

CC Chemokine Ligand 2 (CCL2) is a potent chemoattractant produced by macrophages and activated astrocytes during periods of inflammation within the central nervous system. Increased CCL2 expression is correlated with disease progression and severity, as observed in pulmonary tuberculosis, HCV-related liver disease, and HIV-associated dementia. The CCL2 distal promoter contains an A/G polymorphism at position -2578 and the homozygous -2578 G/G genotype is associated with increased CCL2 production and inflammation. However, the mechanisms that contribute to the phenotypic differences in CCL2 expression are poorly understood. We previously demonstrated that the -2578 G polymorphism creates a TALE homeodomain protein binding site (TALE binding site) for PREP1/PBX2 transcription factors. In this study, we identified the presence of an additional TALE binding site 22 bp upstream of the site created by the -2578 G polymorphism and demonstrated the synergistic effects of the two sites on the activation of the CCL2 promoter. Using chromatin immunoprecipitation (ChIP) assays, we demonstrated increased binding of the TALE proteins PREP1 and PBX2 to the -2578 G allele, and binding of IRF1 to both the A and G alleles. The presence of TALE binding sites that form inverted repeats within the -2578 G allele results in increased transcriptional activation of the CCL2 distal promoter while the presence of only the upstream TALE binding site within the -2578 A allele exerts repression of promoter activity.

Direct activation of human and mouse Oct4 genes using engineered TALE and Cas9 transcription factors

PubMed Central

Hu, Jiabiao; Lei, Yong; Wong, Wing-Ki; Liu, Senquan; Lee, Kai-Chuen; He, Xiangjun; You, Wenxing; Zhou, Rui; Guo, Jun-Tao; Chen, Xiongfong; Peng, Xianlu; Sun, Hao; Huang, He; Zhao, Hui; Feng, Bo

2014-01-01

The newly developed transcription activator-like effector protein (TALE) and clustered regularly interspaced short palindromic repeats/Cas9 transcription factors (TF) offered a powerful and precise approach for modulating gene expression. In this article, we systematically investigated the potential of these new tools in activating the stringently silenced pluripotency gene Oct4 (Pou5f1) in mouse and human somatic cells. First, with a number of TALEs and sgRNAs targeting various regions in the mouse and human Oct4 promoters, we found that the most efficient TALE-VP64s bound around −120 to −80 bp, while highly effective sgRNAs targeted from −147 to −89-bp upstream of the transcription start sites to induce high activity of luciferase reporters. In addition, we observed significant transcriptional synergy when multiple TFs were applied simultaneously. Although individual TFs exhibited marginal activity to up-regulate endogenous gene expression, optimized combinations of TALE-VP64s could enhance endogenous Oct4 transcription up to 30-fold in mouse NIH3T3 cells and 20-fold in human HEK293T cells. More importantly, the enhancement of OCT4 transcription ultimately generated OCT4 proteins. Furthermore, examination of different epigenetic modifiers showed that histone acetyltransferase p300 could enhance both TALE-VP64 and sgRNA/dCas9-VP64 induced transcription of endogenous OCT4. Taken together, our study suggested that engineered TALE-TF and dCas9-TF are useful tools for modulating gene expression in mammalian cells. PMID:24500196

Direct activation of human and mouse Oct4 genes using engineered TALE and Cas9 transcription factors.

PubMed

Hu, Jiabiao; Lei, Yong; Wong, Wing-Ki; Liu, Senquan; Lee, Kai-Chuen; He, Xiangjun; You, Wenxing; Zhou, Rui; Guo, Jun-Tao; Chen, Xiongfong; Peng, Xianlu; Sun, Hao; Huang, He; Zhao, Hui; Feng, Bo

2014-04-01

The newly developed transcription activator-like effector protein (TALE) and clustered regularly interspaced short palindromic repeats/Cas9 transcription factors (TF) offered a powerful and precise approach for modulating gene expression. In this article, we systematically investigated the potential of these new tools in activating the stringently silenced pluripotency gene Oct4 (Pou5f1) in mouse and human somatic cells. First, with a number of TALEs and sgRNAs targeting various regions in the mouse and human Oct4 promoters, we found that the most efficient TALE-VP64s bound around -120 to -80 bp, while highly effective sgRNAs targeted from -147 to -89-bp upstream of the transcription start sites to induce high activity of luciferase reporters. In addition, we observed significant transcriptional synergy when multiple TFs were applied simultaneously. Although individual TFs exhibited marginal activity to up-regulate endogenous gene expression, optimized combinations of TALE-VP64s could enhance endogenous Oct4 transcription up to 30-fold in mouse NIH3T3 cells and 20-fold in human HEK293T cells. More importantly, the enhancement of OCT4 transcription ultimately generated OCT4 proteins. Furthermore, examination of different epigenetic modifiers showed that histone acetyltransferase p300 could enhance both TALE-VP64 and sgRNA/dCas9-VP64 induced transcription of endogenous OCT4. Taken together, our study suggested that engineered TALE-TF and dCas9-TF are useful tools for modulating gene expression in mammalian cells.

49 CFR Appendix B to Subchapter B... - Special Agents

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 5 2013-10-01 2013-10-01 false Special Agents B Appendix B to Subchapter B of Chapter III Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER..., Subch. B, App. B Appendix B to Subchapter B of Chapter III—Special Agents Cautionary note: This appendix...

49 CFR Appendix B to Subchapter B... - Special Agents

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 5 2014-10-01 2014-10-01 false Special Agents B Appendix B to Subchapter B of Chapter III Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER..., Subch. B, App. B Appendix B to Subchapter B of Chapter III—Special Agents Cautionary note: This appendix...

49 CFR Appendix B to Subchapter B... - Special Agents

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 5 2012-10-01 2012-10-01 false Special Agents B Appendix B to Subchapter B of Chapter III Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER..., Subch. B, App. B Appendix B to Subchapter B of Chapter III—Special Agents Cautionary note: This appendix...

The Electronic Revolution in Libraries: Microfilm Deja Vu?

ERIC Educational Resources Information Center

Cady, Susan A.

1990-01-01

Reviews the use of microfilm as an acquisitions and preservation tool in academic libraries, and discusses how this use has fallen short of predictions that microfilm would revolutionize research methodology and scholarly productivity. This history is used to provide cautionary guidance in approaching the era of electronic documentation. (35…

Forest inventory and stratified estimation: a cautionary note

Treesearch

John Coulston

2008-01-01

The Forest Inventory and Analysis (FIA) Program uses stratified estimation techniques to produce estimates of forest attributes. Stratification must be unbiased and stratification procedures should be examined to identify any potential bias. This note explains simple techniques for identifying potential bias, discriminating between sample bias and stratification bias,...

Local and Community History: Some Cautionary Remarks on an Idea Whose Time Has Returned.

ERIC Educational Resources Information Center

Gerber, David A.

1979-01-01

Analyzes past local history movements and addresses benefits and problems for historical studies and history teaching in the current upsurge of interest in local and community history. Concludes that local history must transcend parochialism in order to see the larger picture. (KC)

Mysterious Roving Rocks of Racetrack Playa

NASA Image and Video Library

2017-12-08

The rocks are famous because they move, leaving tell-tale trails in the clay, like this one. This happens at several playa in California and Nevada. There's no record of anybody seeing one of the rocks move, and scientists aren't quite sure how it happens. But they know that it's not the work of animals, gravity, or earthquakes. Photo credit: NASA/GSFC/Cynthia Cheung To read a feature story on the Racetrack Playa go to: www.nasa.gov/topics/earth/features/roving-rocks.html NASA Goddard Space Flight Center is home to the nation's largest organization of combined scientists, engineers and technologists that build spacecraft, instruments and new technology to study the Earth, the sun, our solar system, and the universe. Follow us on Twitter Join us on Facebook

Coyote & Little Turtle = Iisaw Niqw Yongosonhoya: A Traditional Hopi Tale and Coyote & the Winnowing Birds = Iisaw Niqw Tsaayantotaqam Tsiroot: A Traditional Hopi Tale. Original Language Series.

ERIC Educational Resources Information Center

Sekaquaptewa, Emory, Ed.; Pepper, Barbara, Ed.

Intended to promote the preservation of the Hopi language, two illustrated children's books present traditional Hopi tales in bilingual format. Based on a story told by Herschel Talashoema, "Coyote & Little Turtle" tells how Little Turtle tricked Coyote into carrying him from the hot sand that burned his feet to Little Turtle's home in a spring.…

The Emergence of Fairy Tale Literacy: A Multiple Case Study on Promoting Critical Literacy of Children through a Juxtaposed Reading of Classic Fairy Tales and Their Contemporary Disruptive Variants

ERIC Educational Resources Information Center

Li, Chieh-Lan

2010-01-01

Children nowadays perceive fairy tales from a number of sources; however, the strongest prior impressions toward this genre held by most youngsters are still built on the popular mass media-based adaptations such as the animated films or books of fairytale retellings by the Walt Disney Company. In order to make a change to such an undesirable…

Computational Drafting of Plot Structures for Russian Folk Tales.

PubMed

Gervás, Pablo

The plots of stories are known to follow general patterns in terms of their overall structure. This was the basic tenet of structuralist approaches to narratology. Vladimir Propp proposed a procedure for the generation of new tales based on his semi-formal description of the structure of Russian folk tales. This is one of the first existing instances of a creative process described procedurally. The present paper revisits Propp's morphology to build a system that generates instances of Russian folk tales. Propp's view of the folk tale as a rigid sequence of character functions is employed as a plot driver, and some issues that Propp declared relevant but did not explore in detail-such as long-range dependencies between functions or the importance of endings-are given computational shape in the context of a broader architecture that captures all the aspects discussed by Propp. A set of simple evaluation metrics for the resulting outputs is defined inspired on Propp's formalism. The potential of the resulting system for providing a creative story generation system is discussed, and possible lines of future work are discussed.

Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors.

PubMed

Perdigão, Pedro; Gaj, Thomas; Santa-Marta, Mariana; Barbas, Carlos F; Goncalves, Joao

2016-01-01

The presence of replication-competent HIV-1 -which resides mainly in resting CD4+ T cells--is a major hurdle to its eradication. While pharmacological approaches have been useful for inducing the expression of this latent population of virus, they have been unable to purge HIV-1 from all its reservoirs. Additionally, many of these strategies have been associated with adverse effects, underscoring the need for alternative approaches capable of reactivating viral expression. Here we show that engineered transcriptional modulators based on customizable transcription activator-like effector (TALE) proteins can induce gene expression from the HIV-1 long terminal repeat promoter, and that combinations of TALE transcription factors can synergistically reactivate latent viral expression in cell line models of HIV-1 latency. We further show that complementing TALE transcription factors with Vorinostat, a histone deacetylase inhibitor, enhances HIV-1 expression in latency models. Collectively, these findings demonstrate that TALE transcription factors are a potentially effective alternative to current pharmacological routes for reactivating latent virus and that combining synthetic transcriptional activators with histone deacetylase inhibitors could lead to the development of improved therapies for latent HIV-1 infection.

Libraries of Synthetic TALE-Activated Promoters: Methods and Applications.

PubMed

Schreiber, T; Tissier, A

2016-01-01

The discovery of proteins with programmable DNA-binding specificities triggered a whole array of applications in synthetic biology, including genome editing, regulation of transcription, and epigenetic modifications. Among those, transcription activator-like effectors (TALEs) due to their natural function as transcription regulators, are especially well-suited for the development of orthogonal systems for the control of gene expression. We describe here the construction and testing of libraries of synthetic TALE-activated promoters which are under the control of a single TALE with a given DNA-binding specificity. These libraries consist of a fixed DNA-binding element for the TALE, a TATA box, and variable sequences of 19 bases upstream and 43 bases downstream of the DNA-binding element. These libraries were cloned using a Golden Gate cloning strategy making them usable as standard parts in a modular cloning system. The broad range of promoter activities detected and the versatility of these promoter libraries make them valuable tools for applications in the fine-tuning of expression in metabolic engineering projects or in the design and implementation of regulatory circuits. © 2016 Elsevier Inc. All rights reserved.

Live visualization of genomic loci with BiFC-TALE

PubMed Central

Hu, Huan; Zhang, Hongmin; Wang, Sheng; Ding, Miao; An, Hui; Hou, Yingping; Yang, Xiaojing; Wei, Wensheng; Sun, Yujie; Tang, Chao

2017-01-01

Tracking the dynamics of genomic loci is important for understanding the mechanisms of fundamental intracellular processes. However, fluorescent labeling and imaging of such loci in live cells have been challenging. One of the major reasons is the low signal-to-background ratio (SBR) of images mainly caused by the background fluorescence from diffuse full-length fluorescent proteins (FPs) in the living nucleus, hampering the application of live cell genomic labeling methods. Here, combining bimolecular fluorescence complementation (BiFC) and transcription activator-like effector (TALE) technologies, we developed a novel method for labeling genomic loci (BiFC-TALE), which largely reduces the background fluorescence level. Using BiFC-TALE, we demonstrated a significantly improved SBR by imaging telomeres and centromeres in living cells in comparison with the methods using full-length FP. PMID:28074901

Regulation of endogenous human gene expression by ligand-inducible TALE transcription factors.

PubMed

Mercer, Andrew C; Gaj, Thomas; Sirk, Shannon J; Lamb, Brian M; Barbas, Carlos F

2014-10-17

The construction of increasingly sophisticated synthetic biological circuits is dependent on the development of extensible tools capable of providing specific control of gene expression in eukaryotic cells. Here, we describe a new class of synthetic transcription factors that activate gene expression in response to extracellular chemical stimuli. These inducible activators consist of customizable transcription activator-like effector (TALE) proteins combined with steroid hormone receptor ligand-binding domains. We demonstrate that these ligand-responsive TALE transcription factors allow for tunable and conditional control of gene activation and can be used to regulate the expression of endogenous genes in human cells. Since TALEs can be designed to recognize any contiguous DNA sequence, the conditional gene regulatory system described herein will enable the design of advanced synthetic gene networks.

Live visualization of genomic loci with BiFC-TALE.

PubMed

Hu, Huan; Zhang, Hongmin; Wang, Sheng; Ding, Miao; An, Hui; Hou, Yingping; Yang, Xiaojing; Wei, Wensheng; Sun, Yujie; Tang, Chao

2017-01-11

Tracking the dynamics of genomic loci is important for understanding the mechanisms of fundamental intracellular processes. However, fluorescent labeling and imaging of such loci in live cells have been challenging. One of the major reasons is the low signal-to-background ratio (SBR) of images mainly caused by the background fluorescence from diffuse full-length fluorescent proteins (FPs) in the living nucleus, hampering the application of live cell genomic labeling methods. Here, combining bimolecular fluorescence complementation (BiFC) and transcription activator-like effector (TALE) technologies, we developed a novel method for labeling genomic loci (BiFC-TALE), which largely reduces the background fluorescence level. Using BiFC-TALE, we demonstrated a significantly improved SBR by imaging telomeres and centromeres in living cells in comparison with the methods using full-length FP.

State Accountability in the Transition to Common Core. Updated

ERIC Educational Resources Information Center

Sears, Victoria

2014-01-01

The Common Core is at a critical juncture. While many surveys show that support for the standards themselves remains strong, implementation has not been without major challenges. "State Accountability in the Transition to Common Core," a new policy brief from the Thomas B. Fordham Institute, provides cautionary advice about what key…

Making Our Institutional Discourse Sticky: Suggestions for Effective Rhetoric

ERIC Educational Resources Information Center

Harris, Muriel

2010-01-01

In this article, the author offers cautionary advice to help avoid some tempting morasses to unwittingly fall into as well as some more solid ground to stroll along when composing institutional prose. Ultimately, drawing on concepts from the fields of business, linguistics, social psychology, and professional writing, the author wishes to…

Diagnostic ultrasound exposure in man.

PubMed

Gramiak, R

1975-09-01

In his review of the AAPM statement on ultrasound, the author feels that allowing "some" research or demonstration on normal persons in the face of cautionary statements on as yet unknown side effects is an inconsistent position. The use of videotapes and the development of simulators hacked by data banks are offered in place of tissue phantoms.

Employment Protection of School Psychologists: A Cautionary Case

ERIC Educational Resources Information Center

Zirkel, Perry A.

2013-01-01

This article addresses legal issues arising from a district's decision not to renew the employment contract of a 61-year-old school psychologist after 9 years of service. The case focuses on the issues of age discrimination and whistleblowing, although it raises other questions of current relevance to school psychologists, such as the…

Mobile Applications and Decolonization: Cautionary Notes about the Curriculum of Code

ERIC Educational Resources Information Center

Smith, Bryan

2016-01-01

The current generation of students live and learn within a pedagogical milieu saturated by digital technologies. Curriculum scholars have not ignored this, theorizing and critiquing the ways that technology both affords and limits opportunities for students. Notably absent from this conversation, however, is a consideration of how the technologies…

Who (Else) Is the Teacher? Cautionary Notes on Teacher Accountability Systems

ERIC Educational Resources Information Center

Valli, Linda; Croninger, Robert G.; Walters, Kirk

2007-01-01

This article examines a premise underlying teacher accountability policies, namely, that annual student learning gains can be attributed to individual teachers. After analyzing data collected in fourth- and fifth-grade reading and mathematics classes in 18 schools, the authors identify forms of instructional design that rely on multiple teachers.…

To Spray or Not To Spray? A Debate Over DDT.

ERIC Educational Resources Information Center

Dinan, Frank J.; Bieron, Joseph F.

2001-01-01

Presents an activity in which students grapple with the complex issues surrounding the use of DDT to control malaria which affects millions of people in developing nations. Considers risk/benefit analysis and the pre-cautionary principle, two techniques used when making policy decisions involving the impact of science and technology on society.…

Exercise is medicine: some cautionary remarks in principle as well as in practice.

PubMed

Neville, Ross D

2013-08-01

On the basis of extensive research on the relationship between physical activity, exercise and health, as well as strong support from policymakers and practitioners, the "Exercise is Medicine" initiative has become something of a linchpin in the agenda for modern healthcare reform and reflects a broader acceptance that the philosophy of health politics must shift from social engineering to performativity. However, in spite of the avowed commitment to encouraging individuals to take on a more reflexive relation to their health, it remains unclear as to whether an initiative such as this is, unambiguously, a good thing. In this paper, a number of cautionary remarks are made with respect to "Exercise is Medicine" in principle as well as in practice. Firstly, it is argued that equating exercise with medicine is to equate it with a definition of and relation to the body to which it is not entirely akin. And secondly, it is argued that any proposed alignment of the fitness and healthcare industries needs further critical examination, a realigning of interests, and a thorough reconsideration of their suitability of fit.

Fréquence et facteurs de risque maternels de la mort fœtale in utero à Kamina, République Démocratique du Congo

PubMed Central

Kangulu, Ignace Bwana; A'Nkoy, Albert Mwembo Tambwe; Lumbule, John Ngoy; Umba, Elie Kilolo Ngoy; Nzaji, Michel Kabamba; Kayamba, Prosper Kalenga Muenze

2016-01-01

Introduction La mort fœtale in utero constitue un problème fréquent dans la pratique obstétricale. Les objectifs de cette étude étaient de déterminer la fréquence et d'identifier les facteurs de risque de la mort fœtale in utero à l'Hôpital Général de Référence de Kamina. Méthodes L’étude était effectuée en deux temps. En premier lieu, une étude descriptive transversale sur 379 accouchements qui avait permis de déterminer la fréquence de la mort fœtale in utero. La détermination des facteurs de risque était faite à l'aide d'une étude cas-témoins dans laquelle les caractéristiques de 53 morts in utero ont été comparées à 106 témoins constitués des naissances vivantes et à terme. Résultats La fréquence de la mort fœtale in utero à l'Hôpital Général de Référence de Kamina était de 13,9%. Après ajustement, l’âge maternel de plus de 35 ans (OR = 6,23; IC= (1,30-29,80)), l'antécédent de mort fœtale in utero (OR = 3,13; IC= (1,06-9,27)) et la maladie au cours de la grossesse (OR = 31,6, IC= (7,66-130,71)) ont été retenus comme facteurs significativement associés à l'augmentation de la survenue de la mort fœtale. L'instruction élevée de la mère (OR = 0,11; IC= IC= [0,03-0,42]) et la résidence à Kamina (OR = 0,23; IC= (0,08-0,62)) diminuaient ce risque. Conclusion La fréquence de la mort fœtale in utero était de 13,9%. L’âge maternel avancé l'antécédent de mort in utero et la maladie au cours de la grossesse étaient associés à la mort fœtale in utero mais par contre, l'instruction élevée de la femme et la résidence à Kamina diminuaient le risque. La surveillance des gestantes à risque, le dépistage et la prise en charge des maladies pendant la grossesse s'avèrent nécessaires dans la perspective de réduire la fréquence de la mort fœtale in utero dans notre milieu. PMID:27279941

"Dear Bob . . . ."

ERIC Educational Resources Information Center

Kimmel, Eric A.

1980-01-01

A humorous presentation of publisher-to-author correspondence that indicates how contemporary publishers might criticize or reject such works as "Treasure Island,""The Tale of Peter Rabbit,""Little Women," and the Grimm brothers' fairy tales. (ET)

Tale of a Performance Contract

ERIC Educational Resources Information Center

Berson, Minnie Perrin

1971-01-01

Excerpts from Texarkana and Gary: A Tale of Two Performance Contracts," Childhood Education Magazine, March 1971; reports on observations made during visit to Gary, Indiana, school under contract to Behavioral Research Laboratories. (RT)

K-8 Collection.

ERIC Educational Resources Information Center

Web Feet, 2001

2001-01-01

This annotated subject guide to Web sites for grades K-8 focuses on biography, dinosaurs, fairy tales and folk tales, history, math, science, and calendar connections for December observances. Specific grade levels are indicated for each annotation. (LRW)

Expansion of TALE homeobox genes and the evolution of spiralian development.

PubMed

Morino, Yoshiaki; Hashimoto, Naoki; Wada, Hiroshi

2017-12-01

Spiralians, including molluscs, annelids and platyhelminths, share a unique development process that includes the typical geometry of early cleavage and early segregation of cell fate in blastomeres along the animal-vegetal axis. However, the molecular mechanisms underlying this early cell fate segregation are largely unknown. Here, we report spiralian-specific expansion of the three-amino-acid loop extension (TALE) class of homeobox genes. During early development, some of these TALE genes are expressed in staggered domains along the animal-vegetal axis in the limpet Nipponacmea fuscoviridis and the polychaete Spirobranchus kraussii. Inhibition or overexpression of these genes alters the developmental fate of blastomeres, as predicted by the gene expression patterns. These results suggest that the expansion of novel TALE genes plays a critical role in the establishment of a novel cell fate segregation mechanism in spiralians.

Glimpse into Hox and tale regulation of cell differentiation and reprogramming.

PubMed

Cerdá-Esteban, Nuria; Spagnoli, Francesca M

2014-01-01

During embryonic development, cells become gradually restricted in their developmental potential and start elaborating lineage-specific transcriptional networks to ultimately acquire a unique differentiated state. Hox genes play a central role in specifying regional identities, thereby providing the cell with critical information on positional value along its differentiation path. The exquisite DNA-binding specificity of the Hox proteins is frequently dependent upon their interaction with members of the TALE family of homeodomain proteins. In addition to their function as Hox-cofactors, TALE homeoproteins control multiple crucial developmental processes through Hox-independent mechanisms. Here, we will review recent findings on the function of both Hox and TALE proteins in cell differentiation, referring mostly to vertebrate species. In addition, we will discuss the direct implications of this knowledge on cell plasticity and cell reprogramming. Copyright © 2013 Wiley Periodicals, Inc.

The TALE face of Hox proteins in animal evolution.

PubMed

Merabet, Samir; Galliot, Brigitte

2015-01-01

Hox genes are major regulators of embryonic development. One of their most conserved functions is to coordinate the formation of specific body structures along the anterior-posterior (AP) axis in Bilateria. This architectural role was at the basis of several morphological innovations across bilaterian evolution. In this review, we traced the origin of the Hox patterning system by considering the partnership with PBC and Meis proteins. PBC and Meis belong to the TALE-class of homeodomain-containing transcription factors and act as generic cofactors of Hox proteins for AP axis patterning in Bilateria. Recent data indicate that Hox proteins acquired the ability to interact with their TALE partners in the last common ancestor of Bilateria and Cnidaria. These interactions relied initially on a short peptide motif called hexapeptide (HX), which is present in Hox and non-Hox protein families. Remarkably, Hox proteins can also recruit the TALE cofactors by using specific PBC Interaction Motifs (SPIMs). We describe how a functional Hox/TALE patterning system emerged in eumetazoans through the acquisition of SPIMs. We anticipate that interaction flexibility could be found in other patterning systems, being at the heart of the astonishing morphological diversity observed in the animal kingdom.

An engineered tale-transcription factor rescues transcription of factor VII impaired by promoter mutations and enhances its endogenous expression in hepatocytes.

PubMed

Barbon, Elena; Pignani, Silvia; Branchini, Alessio; Bernardi, Francesco; Pinotti, Mirko; Bovolenta, Matteo

2016-06-24

Tailored approaches to restore defective transcription responsible for severe diseases have been poorly explored. We tested transcription activator-like effectors fused to an activation domain (TALE-TFs) in a coagulation factor VII (FVII) deficiency model. In this model, the deficiency is caused by the -94C > G or -61T > G mutation, which abrogate the binding of Sp1 or HNF-4 transcription factors. Reporter assays in hepatoma HepG2 cells naturally expressing FVII identified a single TALE-TF (TF4) that, by targeting the region between mutations, specifically trans-activated both the variant (>100-fold) and wild-type (20-40-fold) F7 promoters. Importantly, in the genomic context of transfected HepG2 and transduced primary hepatocytes, TF4 increased F7 mRNA and protein levels (2- to 3-fold) without detectable off-target effects, even for the homologous F10 gene. The ectopic F7 expression in renal HEK293 cells was modestly affected by TF4 or by TALE-TF combinations. These results provide experimental evidence for TALE-TFs as gene-specific tools useful to counteract disease-causing promoter mutations.

Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors

PubMed Central

Perdigão, Pedro; Gaj, Thomas; Santa-Marta, Mariana; Goncalves, Joao

2016-01-01

The presence of replication-competent HIV-1 –which resides mainly in resting CD4+ T cells–is a major hurdle to its eradication. While pharmacological approaches have been useful for inducing the expression of this latent population of virus, they have been unable to purge HIV-1 from all its reservoirs. Additionally, many of these strategies have been associated with adverse effects, underscoring the need for alternative approaches capable of reactivating viral expression. Here we show that engineered transcriptional modulators based on customizable transcription activator-like effector (TALE) proteins can induce gene expression from the HIV-1 long terminal repeat promoter, and that combinations of TALE transcription factors can synergistically reactivate latent viral expression in cell line models of HIV-1 latency. We further show that complementing TALE transcription factors with Vorinostat, a histone deacetylase inhibitor, enhances HIV-1 expression in latency models. Collectively, these findings demonstrate that TALE transcription factors are a potentially effective alternative to current pharmacological routes for reactivating latent virus and that combining synthetic transcriptional activators with histone deacetylase inhibitors could lead to the development of improved therapies for latent HIV-1 infection. PMID:26933881

The TALE face of Hox proteins in animal evolution

PubMed Central

Merabet, Samir; Galliot, Brigitte

2015-01-01

Hox genes are major regulators of embryonic development. One of their most conserved functions is to coordinate the formation of specific body structures along the anterior-posterior (AP) axis in Bilateria. This architectural role was at the basis of several morphological innovations across bilaterian evolution. In this review, we traced the origin of the Hox patterning system by considering the partnership with PBC and Meis proteins. PBC and Meis belong to the TALE-class of homeodomain-containing transcription factors and act as generic cofactors of Hox proteins for AP axis patterning in Bilateria. Recent data indicate that Hox proteins acquired the ability to interact with their TALE partners in the last common ancestor of Bilateria and Cnidaria. These interactions relied initially on a short peptide motif called hexapeptide (HX), which is present in Hox and non-Hox protein families. Remarkably, Hox proteins can also recruit the TALE cofactors by using specific PBC Interaction Motifs (SPIMs). We describe how a functional Hox/TALE patterning system emerged in eumetazoans through the acquisition of SPIMs. We anticipate that interaction flexibility could be found in other patterning systems, being at the heart of the astonishing morphological diversity observed in the animal kingdom. PMID:26347770

Autobiographical memory functions in young Japanese men and women.

PubMed

Maki, Yoichi; Kawasaki, Yayoi; Demiray, Burcu; Janssen, Steve M J

2015-01-01

The present study examined whether the three major functions of autobiographical memory observed in Western societies (i.e., directing-behaviour, social-bonding and self-continuity) also exist in an East Asian society. Two self-report measures were used to assess the autobiographical memory functions of Japanese men and women. Japanese young adults (N = 451, ages 17-28 years) first completed the original Thinking About Life Experiences (TALE) Questionnaire. They subsequently received three TALE items that represented memory functions and attempted to recall a specific instance of memory recall for each item. Confirmatory factor analyses on the TALE showed that the three functions were replicated in the current sample. However, Japanese participants reported lower levels of all three functions than American participants in a previous study. We also explored whether there was an effect of gender in this Japanese sample. Women reported higher levels of the self-continuity and social-bonding functions than men. Finally, participants recalled more specific instances of memory recall for the TALE items that had received higher ratings on the TALE, suggesting that the findings on the first measure were supported by the second measure. Results are discussed in relation to the functional approach to autobiographical memory in a cross-cultural context.

The Three Tales Chosen, the Establishment of the Texts and the Charting of Deviations, with a Collation of the "Original Tales," the Check Translations, and the Danish and Turkish Texts. Fairytale: An Interdisciplinary Turco-Danish Study of the Collective v. the Individual Nature of the Response to Literature. Report No. 11. Revised.

ERIC Educational Resources Information Center

Dollerup, Cay; And Others

Part of the interdisciplinary Turko-Danish Fairytale Project, this paper provides information about the three fairy tales chosen for study: "The Snake, the Fox, and the Man,""The Gold Apple," and "Per Smed's Whip." Various sections of the paper contain descriptions of the following: (1) the selection procedures, (2)…

Learning from Cities: A Cautionary Note about Urban/Childhood/Nature Entanglements

ERIC Educational Resources Information Center

Morgan, John

2017-01-01

This article examines the urban and pedagogical imaginations that underpin the Editors' call for papers in this special issue of EER. It raises two concerns. The first is that the view of the "urban" that underpins work in this field, whilst offering some new insights, tends to overlook the powerful forces and structures that produce…

Guide to School Renovation and Construction: What You Need To Know To Protect Child and Adult Environmental Health.

ERIC Educational Resources Information Center

Healthy Schools Network, Inc., Albany, NY.

This guide presents cautionary tips for protecting children's health during school renovation and construction projects, the New York state laws regarding school renovation and construction, and the steps the laws require to eliminate dangerous conditions for children during these projects. Included is a checklist of uniform safety standards…

Fire management in some California ecosystems: a cautionary note

Treesearch

Hartmut S. Walter; Teresa Brennan; Christian Albrecht

2005-01-01

Fire has been recognized as a natural and important physical factor in many ecoregions of North America. We wish to point out that our understanding of the biocomplexity of our natural ecosystems is far from complete; in particular, the role of fire in vegetation succession and ecosystem health deserves more scrutiny where biodiversity conservation is a primary or...

Mixed Effects Modeling of Morris Water Maze Data: Advantages and Cautionary Notes

ERIC Educational Resources Information Center

Young, Michael E.; Clark, M. H.; Goffus, Andrea; Hoane, Michael R.

2009-01-01

Morris water maze data are most commonly analyzed using repeated measures analysis of variance in which daily test sessions are analyzed as an unordered categorical variable. This approach, however, may lack power, relies heavily on post hoc tests of daily performance that can complicate interpretation, and does not target the nonlinear trends…

More Light: An Argument for Complexity in Studies of Teaching and Teacher Education.

ERIC Educational Resources Information Center

Florio-Ruane, Susan

2002-01-01

Discusses the complexities of teaching and teacher education, examining circumstances that change the ways in which researchers view teaching and teacher education. The article also presents cautionary thoughts about the tendency to narrow the scope of research to focus only on the spaces immediately relevant to a pressing problem framed by…

Comments on `A Cautionary Note on the Interpretation of EOFs'.

NASA Astrophysics Data System (ADS)

Behera, Swadhin K.; Rao, Suryachandra A.; Saji, Hameed N.; Yamagata, Toshio

2003-04-01

The misleading aspect of the statistical analyses used in Dommenget and Latif, which raises concerns on some of the reported climate modes, is demonstrated. Adopting simple statistical techniques, the physical existence of the Indian Ocean dipole mode is shown and then the limitations of varimax and regression analyses in capturing the climate mode are discussed.

For Whom Does Language Death Toll? Cautionary Notes from the Basque Case

ERIC Educational Resources Information Center

Echeverria, Begona

2010-01-01

In this article, I show that despite a seemingly inclusive, language-based identity promoted in schools and pedagogical materials, Basque identity and language are embedded with social histories that exclude large swaths of the would-be Basque nation: women and second language learners of Basque. To the extent that these processes continue to…

Bertrand's Paradox: A Physical Way out along the Lines of Buffon's Needle Throwing Experiment

ERIC Educational Resources Information Center

Di Porto, P.; Crosignani, B.; Ciattoni, A.; Liu, H. C.

2011-01-01

Bertrand's paradox (Bertrand 1889 "Calcul des Probabilites" (Paris: Gauthier-Villars)) can be considered as a cautionary memento, to practitioners and students of probability calculus alike, of the possible ambiguous meaning of the term "at random" when the sample space of events is continuous. It deals with the existence of different possible…

Online Periodic Table: A Cautionary Note

ERIC Educational Resources Information Center

Izci, Kemal; Barrow, Lloyd H.; Thornhill, Erica

2013-01-01

The purpose of this study was (a) to evaluate ten online periodic table sources for their accuracy and (b) to compare the types of information and links provided to users. Limited studies have been reported on online periodic table (Diener and Moore 2011; Slocum and Moore in "J Chem Educ" 86(10):1167, 2009). Chemistry students'…

16 CFR 1631.34 - Small carpets and rugs not meeting acceptance criterion.

Code of Federal Regulations, 2011 CFR

2011-01-01

... proximity to the edge of the small carpet or rug. (b) Such cautionary statements shall also appear in a... or effect the sale of small carpets or rugs shall be labeled with the information required by this... samples, swatches, or specimens used to promote or effect the sale thereof, which is not in compliance...

16 CFR 1631.34 - Small carpets and rugs not meeting acceptance criterion.

Code of Federal Regulations, 2014 CFR

2014-01-01

... proximity to the edge of the small carpet or rug. (b) Such cautionary statements shall also appear in a... or effect the sale of small carpets or rugs shall be labeled with the information required by this... samples, swatches, or specimens used to promote or effect the sale thereof, which is not in compliance...

16 CFR § 1631.34 - Small carpets and rugs not meeting acceptance criterion.

Code of Federal Regulations, 2013 CFR

2013-01-01

... proximity to the edge of the small carpet or rug. (b) Such cautionary statements shall also appear in a... or effect the sale of small carpets or rugs shall be labeled with the information required by this... samples, swatches, or specimens used to promote or effect the sale thereof, which is not in compliance...

16 CFR 1631.34 - Small carpets and rugs not meeting acceptance criterion.

Code of Federal Regulations, 2012 CFR

2012-01-01

... proximity to the edge of the small carpet or rug. (b) Such cautionary statements shall also appear in a... or effect the sale of small carpets or rugs shall be labeled with the information required by this... samples, swatches, or specimens used to promote or effect the sale thereof, which is not in compliance...

Two groups of phenylalanine biosynthetic operon leader peptides genes: a high level of apparently incidental frameshifting in decoding Escherichia coli pheL

PubMed Central

Gurvich, Olga L.; Näsvall, S. Joakim; Baranov, Pavel V.; Björk, Glenn R.; Atkins, John F.

2011-01-01

The bacterial pheL gene encodes the leader peptide for the phenylalanine biosynthetic operon. Translation of pheL mRNA controls transcription attenuation and, consequently, expression of the downstream pheA gene. Fifty-three unique pheL genes have been identified in sequenced genomes of the gamma subdivision. There are two groups of pheL genes, both of which are short and contain a run(s) of phenylalanine codons at an internal position. One group is somewhat diverse and features different termination and 5′-flanking codons. The other group, mostly restricted to Enterobacteria and including Escherichia coli pheL, has a conserved nucleotide sequence that ends with UUC_CCC_UGA. When these three codons in E. coli pheL mRNA are in the ribosomal E-, P- and A-sites, there is an unusually high level, 15%, of +1 ribosomal frameshifting due to features of the nascent peptide sequence that include the penultimate phenylalanine. This level increases to 60% with a natural, heterologous, nascent peptide stimulator. Nevertheless, studies with different tRNAPro mutants in Salmonella enterica suggest that frameshifting at the end of pheL does not influence expression of the downstream pheA. This finding of incidental, rather than utilized, frameshifting is cautionary for other studies of programmed frameshifting. PMID:21177642

Using Jack Tales in a Second Grade Class.

ERIC Educational Resources Information Center

Brown, Doris

1987-01-01

Describes a project in which Kentucky second grades developed puppet shows and photography activities based on traditional Appalachian oral tales. Discusses student progress in language arts skills, creativity, use of audiovisual equipment, and group cooperation. (SV)

Unoriginal tales

NASA Astrophysics Data System (ADS)

Sudbery, Tony

2012-03-01

In his article "Other-worldly tales" (December 2011 pp18-19), Robert P Crease describes Hugh Everett's idea of branching universes or "many worlds" as "one of the strangest ideas in the history of thought, and the inspiration for many science-fiction stories".

A multiplexable TALE-based binary expression system for in vivo cellular interaction studies.

PubMed

Toegel, Markus; Azzam, Ghows; Lee, Eunice Y; Knapp, David J H F; Tan, Ying; Fa, Ming; Fulga, Tudor A

2017-11-21

Binary expression systems have revolutionised genetic research by enabling delivery of loss-of-function and gain-of-function transgenes with precise spatial-temporal resolution in vivo. However, at present, each existing platform relies on a defined exogenous transcription activator capable of binding a unique recognition sequence. Consequently, none of these technologies alone can be used to simultaneously target different tissues or cell types in the same organism. Here, we report a modular system based on programmable transcription activator-like effector (TALE) proteins, which enables parallel expression of multiple transgenes in spatially distinct tissues in vivo. Using endogenous enhancers coupled to TALE drivers, we demonstrate multiplexed orthogonal activation of several transgenes carrying cognate variable activating sequences (VAS) in distinct neighbouring cell types of the Drosophila central nervous system. Since the number of combinatorial TALE-VAS pairs is virtually unlimited, this platform provides an experimental framework for highly complex genetic manipulation studies in vivo.

Exploring the transcription activator-like effectors scaffold versatility to expand the toolbox of designer nucleases

PubMed Central

2014-01-01

Background The past decade has seen the emergence of several molecular tools that render possible modification of cellular functions through accurate and easy addition, removal, or exchange of genomic DNA sequences. Among these technologies, transcription activator-like effectors (TALE) has turned out to be one of the most versatile and incredibly robust platform for generating targeted molecular tools as demonstrated by fusion to various domains such as transcription activator, repressor and nucleases. Results In this study, we generated a novel nuclease architecture based on the transcription activator-like effector scaffold. In contrast to the existing Tail to Tail (TtT) and head to Head (HtH) nuclease architectures based on the symmetrical association of two TALE DNA binding domains fused to the C-terminal (TtT) or N-terminal (HtH) end of FokI, this novel architecture consists of the asymmetrical association of two different engineered TALE DNA binding domains fused to the N- and C-terminal ends of FokI (TALE::FokI and FokI::TALE scaffolds respectively). The characterization of this novel Tail to Head (TtH) architecture in yeast enabled us to demonstrate its nuclease activity and define its optimal target configuration. We further showed that this architecture was able to promote substantial level of targeted mutagenesis at three endogenous loci present in two different mammalian cell lines. Conclusion Our results demonstrated that this novel functional TtH architecture which requires binding to only one DNA strand of a given endogenous locus has the potential to extend the targeting possibility of FokI-based TALE nucleases. PMID:24997498

Selective recognition of N4-methylcytosine in DNA by engineered transcription-activator-like effectors.

PubMed

Rathi, Preeti; Maurer, Sara; Summerer, Daniel

2018-06-05

The epigenetic DNA nucleobases 5-methylcytosine (5mC) and N 4-methylcytosine (4mC) coexist in bacterial genomes and have important functions in host defence and transcription regulation. To better understand the individual biological roles of both methylated nucleobases, analytical strategies for distinguishing unmodified cytosine (C) from 4mC and 5mC are required. Transcription-activator-like effectors (TALEs) are programmable DNA-binding repeat proteins, which can be re-engineered for the direct detection of epigenetic nucleobases in user-defined DNA sequences. We here report the natural, cytosine-binding TALE repeat to not strongly differentiate between 5mC and 4mC. To engineer repeats with selectivity in the context of C, 5mC and 4mC, we developed a homogeneous fluorescence assay and screened a library of size-reduced TALE repeats for binding to all three nucleobases. This provided insights into the requirements of size-reduced TALE repeats for 4mC binding and revealed a single mutant repeat as a selective binder of 4mC. Employment of a TALE with this repeat in affinity enrichment enabled the isolation of a user-defined DNA sequence containing a single 4mC but not C or 5mC from the background of a bacterial genome. Comparative enrichments with TALEs bearing this or the natural C-binding repeat provides an approach for the complete, programmable decoding of all cytosine nucleobases found in bacterial genomes.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'. © 2018 The Author(s).

"Thou" and "Ye" in Chaucer's "Clerk's Tale."

ERIC Educational Resources Information Center

Wilcockson, Colin

1980-01-01

Examines the use of the second person pronoun in Chaucer's "Clerk's Tale" to demonstrate that students of medieval texts may well miss important areas of meaning if they fail to give adequate attention to the historical study of language. (GT)

The Fairy-Folk Tale in Media Art: Reflections of Disney and Duvall.

ERIC Educational Resources Information Center

Molloy, Toni

1988-01-01

Focuses on Walt Disney and Shelley Duvall, mass media producers who furnish children with fairy-folklore. Compares and contrasts what Disney and Duvall do and do not convey through their fairy-folk tales. (MS)

A unique stylopod patterning mechanism by Shox2-controlled osteogenesis

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

Ye, Wenduo; Song, Yingnan; Huang, Zhen

Here, vertebrate appendage patterning is programmed by Hox-TALE factorbound regulatory elements. However, it remains unclear which cell lineages are commissioned by Hox-TALE factors to generate regional specific patterns and whether other Hox-TALE co-factors exist. In this study, we investigated the transcriptional mechanisms controlled by the Shox2 transcriptional regulator in limb patterning. Harnessing an osteogenic lineage-specific Shox2 inactivation approach we show that despite widespread Shox2 expression in multiple cell lineages, lack of the stylopod observed upon Shox2 deficiency is a specific result of Shox2 loss of function in the osteogenic lineage. ChIP-Seq revealed robust interaction of Shox2 with cis-regulatory enhancers clusteringmore » around skeletogenic genes that are also bound by Hox-TALE factors, supporting a lineage autonomous function of Shox2 in osteogenic lineage fate determination and skeleton patterning. Pbx ChIP-Seq further allowed the genome-wide identification of cis-regulatory modules exhibiting co-occupancy of Pbx, Meis and Shox2 transcriptional regulators. Integrative analysis of ChIP-Seq and RNA-Seq data and transgenic enhancer assays indicate that Shox2 patterns the stylopod as a repressor via interaction with enhancers active in the proximal limb mesenchyme and antagonizes the repressive function of TALE factors in osteogenesis.« less

Fairy-tale planet: creative science writing for children

NASA Astrophysics Data System (ADS)

Lanza, Tiziana; D'Addezio, Giuliana

2017-04-01

During public events organized by our Institute sometimes we have predisposed a corner to entertain primary school children with fairy-tales about the planet. In that occasion we realized that even if children could take part in other activities more in fashion such as laboratories, theatre performances, exhibits, they were very attracted by fairy tales, such an "ancient" tradition. This year within the projects "alternanza scuola-lavoro" we are planning to involve also the students of the secondary schools to learn themselves how to animate a fairy-tale corner for children. The "alternanza scuola lavoro" (interchange school/work) has been recently introduced in the Italian school as a methodology for implementing the second cycle teaching. The general purpose is to ensure that 15 to 18 years old students, beside the access to basic knowledge, can acquire skills in the employment and real work environments experiencing other teaching methods based both on knowledge and know-how. We will then start a new adventure by investigating what will be the best way to introduce children to creative science writing for the planet. The aim would be that of creating a format suitable for children either for writing all together a planet fairy-tale in class, or individually. The final goal is to raise awareness about the environmental problems by stimulating in scholars their own creativity.

A unique stylopod patterning mechanism by Shox2-controlled osteogenesis

DOE PAGES

Ye, Wenduo; Song, Yingnan; Huang, Zhen; ...

2016-06-10

Here, vertebrate appendage patterning is programmed by Hox-TALE factorbound regulatory elements. However, it remains unclear which cell lineages are commissioned by Hox-TALE factors to generate regional specific patterns and whether other Hox-TALE co-factors exist. In this study, we investigated the transcriptional mechanisms controlled by the Shox2 transcriptional regulator in limb patterning. Harnessing an osteogenic lineage-specific Shox2 inactivation approach we show that despite widespread Shox2 expression in multiple cell lineages, lack of the stylopod observed upon Shox2 deficiency is a specific result of Shox2 loss of function in the osteogenic lineage. ChIP-Seq revealed robust interaction of Shox2 with cis-regulatory enhancers clusteringmore » around skeletogenic genes that are also bound by Hox-TALE factors, supporting a lineage autonomous function of Shox2 in osteogenic lineage fate determination and skeleton patterning. Pbx ChIP-Seq further allowed the genome-wide identification of cis-regulatory modules exhibiting co-occupancy of Pbx, Meis and Shox2 transcriptional regulators. Integrative analysis of ChIP-Seq and RNA-Seq data and transgenic enhancer assays indicate that Shox2 patterns the stylopod as a repressor via interaction with enhancers active in the proximal limb mesenchyme and antagonizes the repressive function of TALE factors in osteogenesis.« less

Generation of TALE-Based Designer Epigenome Modifiers.

PubMed

Nitsch, Sandra; Mussolino, Claudio

2018-01-01

Manipulation of gene expression can be facilitated by editing the genome or the epigenome. Precise genome editing is traditionally achieved by using designer nucleases which are generally exploited to eliminate a specific gene product. Upon the introduction of a site-specific DNA double-strand break (DSB) by the nuclease, endogenous DSB repair mechanisms are in turn harnessed to induce DNA sequence changes that can result in target gene inactivation. Minimal off-target effects can be obtained by endowing designer nucleases with the highly specific DNA-binding domain (DBD) derived from transcription activator-like effectors (TALEs). In contrast, epigenome editing allows gene expression control without inducing changes in the DNA sequence by specifically altering epigenetic marks, as histone tails modifications or DNA methylation patterns within promoter or enhancer regions. Importantly, this approach allows both up- and downregulation of the target gene expression, and the effect is generally reversible. TALE-based designer epigenome modifiers combine the high specificity of TALE-derived DBDs with the power of epigenetic modifier domains to induce fast and long-lasting changes in the epigenetic landscape of a target gene and control its expression. Here we provide a detailed description for the generation of TALE-based designer epigenome modifiers and of a suitable reporter cell line to easily monitor their activity.

The Celestial Bodies in Traditional Armenian Nuptial Songs of Praise

NASA Astrophysics Data System (ADS)

Tigranyan, Marianna

2016-12-01

The universe and its structure have occupied people's minds since the beginning of time. The myths and legends of the ancient cultures are replete with tales about the myriad celestial bodies, planets and stars. Back then, the Ancient Sumerians were phenomenally successful in astronomy; their extensive knowledge is effectively used by astronomers today. The deities were featured as heavenly bodies and were eulogized and revered by the peoples of the Ancient World. At Armenian wedding ceremonies, the groom - traditionally the Crown wearer - was often likened to the Sun, and the bride to the Moon, or sometimes Venus. The newly-married couple was glorified by delightful songs of praise.

Sex Ed...And the Reds? Reconsidering the Anaheim Battle over Sex Education, 1962-1969

ERIC Educational Resources Information Center

Mehlman, Natalia

2007-01-01

By December 1968, the Anaheim Family Life and Sex Education (FLSE) program, celebrated since its formal introduction in 1965 as one of the most progressive in the nation, was being smeared as communistic and perverse. Local activists in this Orange County city had been congregating in hotel rooms and homes, screening cautionary films for the…

Windigo Ways: Eating and Excess in Louise Erdrich's "The Antelope Wife"

ERIC Educational Resources Information Center

Tharp, Julie

2003-01-01

The cautionary figure of windigo has lurked at the edges of Louise Erdrich's writing since her first collection of poems in 1984. In "The Antelope Wife" it finally emerges into full view. A windigo is defined as a cannibalistic monster set loose by human greed, envy, and jealousy. Traditional Ojibwe windigo stories usually focus on the starving…

Variation among pinyon-juniper woodlands: A cautionary note

Treesearch

Matthew A. Williamson

2008-01-01

(Please note, this is an abstract only) The recent emphasis on ecological restoration of forests has forced both scientists and managers to address the idea of the "natural range of variability" of their systems of study. Indeed, much work has been done to identify this range in the ponderosa pine systems of the West and to use that information to develop...

Eta- and Partial Eta-Squared in L2 Research: A Cautionary Review and Guide to More Appropriate Usage

ERIC Educational Resources Information Center

Norouzian, Reza; Plonsky, Luke

2018-01-01

Eta-squared (?[superscript 2]) and partial eta-squared (?[subscript p][superscript 2]) are effect sizes that express the amount of variance accounted for by one or more independent variables. These indices are generally used in conjunction with ANOVA, the most commonly used statistical test in second language (L2) research (Plonsky, 2013).…

Incidental captures of birds in small mammal traps: a cautionary note for interdisciplinary studies.

Treesearch

David L. Waldien; Miranda M. Cooley; Jennifer Weikel; John P. Hayes; Chris C. Maguire; Tom Manning; Thomas J. Maier

2004-01-01

Although benefits of interdisciplinary studies are numerous, potential exists for data acquisition for some aspects of such studies to impact data acquisition for other aspects. This may be particularly true in studies involving both trapping of small mammals and assessment of bird populations. We summarize the incidence of birds captured during 8 research projects in...

Baby Fat May Be Cute, but Chubby Kids Could Be in Jeopardy, and for Children with Disabilities...

ERIC Educational Resources Information Center

Waldman, H. Barry; Perlman, Steven P.

2007-01-01

Baby fat may be cute, but chubby kids could be in imminent health jeopardy. This cautionary advice is most certainly extended to the parents of children with special needs. This article examines the association of childhood obesity with the development of diabetes and discusses the prevalence of obesity among individuals with intellectual…

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

Not Available

This manual of the Chemical Hazard Response Information System (CHRIS) has been developed to present current information and assist on-scene coordinators (OSC) on techniques, equipment, and systems that are available to combat and minimize the damage that can be expected when a hazardous chemical is discharged into navigable waters. The handbook describes the content and use of CHRIS and discusses the causes of accidental discharges of hazardous chemicals. It provides a quick reference guide to the selection of response methods and describes these methods in detail. The handbook is also complemented by an appendix containing a review of the state-of-the-artmore » response equipment and systems and a comprehensive catalogue of response equipment. In this handbook response methods are divided into two categories: cautionary and corrective. Cautionary responses, which should be promptly applied to preserve human and animal life, include restricting entry into the area affected by the discharge and use of the water polluted by the discharge, as well as evacuation of threatened areas. Corrective responses include methods of stopping or reducing a further discharge of the chemical, containment procedures, and methods of collection, recovery, and treatment. Methods of cleaning an affected shoreline and treatment of an exposed waterfront are also described.« less

Can eyewitnesses correct for external influences on their lineup identifications? The actual/counterfactual assessment paradigm.

PubMed

Charman, Steve D; Wells, Gary L

2008-03-01

Real-world eyewitnesses are often asked whether their lineup responses were affected by various external influences, but it is unknown whether they can accurately answer these types of questions. The witness-report-of-influence mental-correction model is proposed to explain witnesses' reports of influence. Two experiments used a new paradigm (the actual/counterfactual paradigm) to examine eyewitnesses' abilities to report accurately on the influence of lineup manipulations. Eyewitnesses were administered either confirming feedback or no feedback (Experiment 1, n = 103), or a cautionary instruction or no cautionary instruction (Experiment 2, n = 114). Eyewitnesses then gave actual responses (retrospective confidence, view, and attention measures in Experiment 1; identification decision in Experiment 2) as well as counterfactual responses stating how they would have responded in the alternative condition. Results across both studies showed an asymmetric estimation of influence pattern: Eyewitnesses who received an influencing manipulation estimated significantly less of a change in their responses than eyewitnesses who did not receive an influencing manipulation. A 48-hr delay between actual and counterfactual responses did not moderate any effects. Results are explained by witnesses' implicit theories of influence. PsycINFO Database Record (c) 2008 APA, all rights reserved

Two Native American Near-Death Experiences.

ERIC Educational Resources Information Center

Schorer, C. E.

1986-01-01

Discusses two tales of near-death experiences from the Chippewas in Michigan during the 1820s with reference to local origin, influence of White American culture, and universality. One tale has autoscopic, specifically Native American elements while the other contains elements of the transcendental type. (Author/NRB)

Psychoanalysis and detective fiction: a tale of Freud and criminal storytelling.

PubMed

Yang, Amy

2010-01-01

Much has been written about Freud's influence on popular culture. This article addresses the influence of literature on Freud's psychoanalytical theory, specifically the role that modern detective fiction played in shaping Freudian theory. Edgar Allan Poe gave Freud the literary precedent; Sir Arthur Conan Doyle's creation Sherlock Holmes gave him the analytical model. In turn, the world of crime story-telling embedded Freudian theories in subsequent forms, spinning the tales of crime into a journey into the human mind. As these tales were popularized on the silver screen in the early 20th century, psychoanalytical ideas moved from the lecture halls into the cultural mainstream.

Genome Editing in Rats Using TALE Nucleases.

PubMed

Tesson, Laurent; Remy, Séverine; Ménoret, Séverine; Usal, Claire; Thinard, Reynald; Savignard, Chloé; De Cian, Anne; Giovannangeli, Carine; Concordet, Jean-Paul; Anegon, Ignacio

2016-01-01

The rat is an important animal model to understand gene function and model human diseases. Since recent years, the development of gene-specific nucleases has become important for generating new rat models of human diseases, to analyze the role of genes and to generate human antibodies. Transcription activator-like (TALE) nucleases efficiently create gene-specific knockout rats and lead to the possibility of gene targeting by homology-directed recombination (HDR) and generating knock-in rats. We describe a detailed protocol for generating knockout and knock-in rats via microinjection of TALE nucleases into fertilized eggs. This technology is an efficient, cost- and time-effective method for creating new rat models.

Creative Thinking with Fairy Tales.

ERIC Educational Resources Information Center

Flack, Jerry

2001-01-01

This article discusses how creative thinking can be encouraged in students through such classic tools as brainstorming and the productive thinking elements of fluency, flexibility, originality, and elaboration. It describes how fairy tales can be used to foster these thinking skills and suggests classroom activities. (Contains two references.) (CR)

Black Cinderella: Multicultural Literature and School Curriculum

ERIC Educational Resources Information Center

Yenika-Agbaw, Vivian

2014-01-01

This article discusses diversity issues evident in fairy tales and explores the pedagogical implications for adding counter-narratives in the school curriculum. Critical Race Theory is employed. In order to uncover contradictory discourses of race within Black cultures, four Africana (African, African American, and Caribbean) Cinderella tale types…

Generation of TALE nickase-mediated gene-targeted cows expressing human serum albumin in mammary glands.

PubMed

Luo, Yan; Wang, Yongsheng; Liu, Jun; Cui, Chenchen; Wu, Yongyan; Lan, Hui; Chen, Qi; Liu, Xu; Quan, Fusheng; Guo, Zekun; Zhang, Yong

2016-02-08

Targeting exogenous genes at milk protein loci via gene-targeting technology is an ideal strategy for producing large quantities of pharmaceutical proteins. Transcription-activator-like effector (TALE) nucleases (TALENs) are an efficient genome-editing tool. However, the off-target effects may lead to unintended gene mutations. In this study, we constructed TALENs and TALE nickases directed against exon 2 of the bovine β-lactoglobulin (BLG) locus. The nickases can induce a site-specific DNA single-strand break, without inducing double-strand break and nonhomologous end joining mediated gene mutation, and lower cell apoptosis rate than TALENs. After co-transfecting the bovine fetal fibroblasts with human serum albumin (HSA) gene-targeting vector and TALE nickase expression vectors, approximately 4.8% (40/835) of the cell clones contained HSA at BLG locus. Unexpectedly, one homozygous gene-targeted cell clone (1/835, 0.1%) was obtained by targeting both alleles of BLG in a single round of transfection. The recombinant protein mimicking the endogenous BLG was highly expressed and correctly folded in the mammary glands of the targeted cows, and the expression level of HSA was significantly increased in the homozygous targeted cows. Results suggested that the combination of TALE nickase-mediated gene targeting and somatic cell nuclear transfer is a feasible and safe approach in producing gene-targeted livestock.