Run In Conjunction Research Articles

Ncrna-a3 Epigenetically Regulates TAL1 and Its Target Genes to Drive Erythroid Differentiation

Erythropoiesis is the development of enucleated red blood cells from multipotent hematopoietic stem cells. This complex process is tightly regulated by the dynamic changes in occupancy of tissue specific transcription factors (TFs) that activate and repress genes appropriately. TAL1, a critical regulator is expressed throughout the development of mature erythroblasts from multi-progenitors. Loss of TAL1 leads to defective erythropoiesis. As opposed to TAL1's role in erythropoiesis, itis an extraneous factor in developing lymphoid cells and aberrant expression of TAL1 in T-cells is associated with T-ALL. The differential regulation during normal and malignant hematopoiesis remains largely unclear. We found that a distil RNA - ncRNA-a3, is transcribed from erythroid specific enhancer, 50kbp downstream of the TAL1 TSS. We hypothesized that ncRNA-a3 plays an important role in regulating TAL1 and its target gene transcription in an erythroid specific manner. To test this hypothesis, we examine the regulatory potential of ncRNA-a3 towards the activation of TAL1 expression in the context of hematopoiesis and leukemogenesis. We used RNA interference to deplete ncRNA-a3 expression across several hematopoietic and leukemic cells. The decrease in ncRNA-a3 resulted in significant reduction of TAL1 transcript and protein levels in hematopoietic cells while TAL1 transcripts showed little or no reduction in leukemic cells. Subsequently, transcriptomic profile changes in erythroleukemic K562 cells showed downregulation of erythroid specific targets of TAL1. To ascertain the role of ncRNA-a3 in erythropoiesis, we used siRNA against ncRNA-a3 in primary CD34+ cells and subjected cells to differentiation. Quantification of early and late erythroblasts by colony forming assay and flow cytometry indicated impaired erythroid differentiation and maturation in orthochromatic and polychromatic stages. Further, RNA-seq analysis of ncRNA-a3 knockdown cells revealed defects in globin gene function, heme biosynthesis and nucleosome condensation compared to control CD34+ cells during time course EPO induced erythroid differentiation. Mechanistically, we observed ncRNA-a3s occupancy at TAL1 regulatory regions from ChIRP-qPCR across TAL1 locus. NG Capture-C data depicting changes in interaction frequencies indicated that ncRNA-a3 maintains canonical interactions at the TAL1 locus. Knockdown of ncRNA-a3 negatively impacted the chromatin accessibility in TAL1 and TAL1 target loci. Perturbation of chromatin landscape affected TAL1 and TAL1 binding partner - P300 and BRG1 occupancy at TAL1 target sites. To distinguish reduced TAL1 binding as a consequence of lower levels of TAL1, from RNA dependent binding of TAL1, we examined TAL1, P300 and BRG1 chromatin occupancy through Cut&Run in conjunction with RNase treatment. Effective depletion of global RNAs resulted in reduced enrichment of TAL1, P300 and BRG1 bound fragments indicating possible RNA dependent binding of TAL1 and its cofactors. TAL1 coimmunoprecipitation using RNase treatment (1) and ncRNA-a3 KD (2), demonstrated that TAL1s interaction with P300 and BRG1 is RNA dependent, but ncRNA-a3 independent. RNA-IP results further confirmed that ncRNA-a3 is associated with TAL1 through its interacting epigenetic cofactors P300 and BRG1. Together, our data indicate that although RNA dependent binding of TAL1 and its epigenetic cofactors is cell type or target locus specific, ncRNA-a3 modulates the occupancy of TAL1, P300 and BRG1 at the TAL1 locus during erythroid specific TAL1 transcription.

It Is Time to Go Public

Changes in modern society are rapid and complex and give rise to social problems such as crime. The relevance of community policing is derived from the need to facilitate robust relationships and mutual information flow between the police and the public. A £30 million UK Department for International Development (UK-DFID) overseeing a community policing initiative run in conjunction with the British Council's Security Justice and Growth in Nigeria did not achieve the desired community safety on account of the wide communication gaps between the security providers and the public in Nigeria. In 2004 at the presidential address to the American Sociological Association, Burawoy introduced the concept of public sociology involving taking sociology to the public audience. Adopting the Michael Burawoy's public sociology theoretical perspective, this paper explores the need and possibility of taking ideas of community policing to the public domain in Nigeria.

Study of SO Pollution in the Middle East Using MERRA‐2, CAMS Data Assimilation Products, and High‐Resolution WRF‐Chem Simulations

AbstractOil recovery, power generation, water desalination, gas flaring, and traffic are the main contributors to SO emissions in the Middle East (ME). Satellite observations suggest that the traditional emission inventories do not account for multiple SO emission sources in the ME. This study aims to evaluate the most frequently used SO emission data sets over the ME by comparing high‐resolution regional model simulations and meteorology/chemistry assimilation products, MERRA‐2 and CAMS, with satellite and available ground‐based air‐quality observations. Here, we employ the WRF‐Chem‐3.7.1 regional meteorology‐chemistry model and conduct simulations for the period 2015–2016 with 10 km grid spacing using HTAP‐2.2 emission data sets and the new OMI‐HTAP data, which is based on the combination of the near‐surface SO emissions taken from the HTAP‐2.2 inventory with strong (>30 kt/year) SO point sources obtained from the satellite Ozone Monitoring Instrument (OMI) observations. We find that conventional emission inventories (EDGAR‐4.2, MACCity, and HTAP‐2.2) have uncertainties in the location and magnitude of SO sources in the ME and significantly underestimate SO emissions in the Arabian Gulf. The WRF‐Chem, run in conjunction with the new OMI‐HTAP emissions, improves comparisons between the satellite and ground‐based SO observations. Our simulations show that SO surface concentrations in Jeddah and Riyadh frequently exceed European air‐quality limits. The ME generates about 10% of global anthropogenic SO emissions, on par with India. Therefore, the development of effective emission controls and improvement of air‐quality monitoring in the ME are urgently needed.

Symmetry Analysis of an Interest Rate Derivatives PDE Model in Financial Mathematics

We perform Lie symmetry analysis to a zero-coupon bond pricing equation whose price evolution is described in terms of a partial differential equation (PDE). As a result, using the computer software package SYM, run in conjunction with Mathematica, a new family of Lie symmetry group and generators of the aforementioned pricing equation are derived. We furthermore compute the exact invariant solutions which constitute the pricing models for the bond by making use of the derived infinitesimal generators and the associated similarity reduction equations. Using known solutions, we again compute more solutions via group point transformations.

The thinking behind the action (learning)

Purpose The purpose of this paper is to report on an action learning (AL) approach to curriculum design and delivery of a two-year part-time executive masters program, facilitated in part through a longitudinal work-based action research project. Program participants were a mix of mid- to senior managers operating in both the public and private sector and business owners, and all were in full-time employment. Design/methodology/approach This paper presents findings relating to participant and tutor perspectives of the program design, structure, and content. It also chronicles an AL tutor initiative run in conjunction with the inaugural program delivery, established to provide a collegial approach to learner facilitation, and to enable a research informed model of practice. Findings Findings suggest that the program allowed for greater action-reflection among and across all contributors (students, tutors, and program managers), and facilitated cross-pollination of AL perspectives, thus strengthening the interaction between practitioner and academic, and among academics themselves. Furthermore, the early involvement of tutors informed the work-based research project and larger AL program, and facilitated a matching of research interests between practitioner and tutor. Originality/value These findings suggest that an action-based model of knowledge transfer and development offers significant learning benefits to those partaking in an executive development program, resulting in the following insights: executive needs better served using a learner-centric approach; problem-oriented work-based assessment affords theory–practice balance; there is evidence of action-reflection “contagion” among all contributors; and the presented AL cycle has potential value in the conceptualization of reflective action.

Family planning in a rural setting in Uganda, the USHAPE initiative.

BackgroundThe total fertility rate in Uganda is 5.9 children per woman, and women admit to having nearly two more children than they actually want. The maternal mortality rate remains stubbornly high. Family planning saves lives. It prevents maternal deaths by delaying motherhood, helping women limit their family size and avoid unwanted pregnancies. It also reduces infant mortality.SettingUSHAPE (Ugandan Sexual Health and Pastoral Education) is an initiative run in conjunction with the Royal College of General Practitioners in south-west Uganda. USHAPE aims to disseminate positive messages about modern contraception in an attempt to dispel fears and misconceptions and address the high rate of unmet need.QuestionThe aim was to determine the rate of unmet need for family planning among women of reproductive age in the population local of Kisiizi hospital and to use the successful USHAPE model to train health workers to address this need.Methods100 patients were screened in the outpatient department to determine the level of unmet need by asking 2 questions. Level 1 training aims enhance every staff member’s knowledge, so that the responsibility for family planning is adopted by the whole institution. Level 2 trains clinicians to become full family planning providers, with the necessary communication, educational and practical skills.ResultsThe screening for unmet need for contraception revealed that 51% have an unmet need, which is higher than the national average of 38%. Sixty-eight members of staff at Kisiizi trained to a basic level and a further 32 staff have been trained to Level 2 higher level.Conclusions/DiscussionThe USHAPE approach has begun to tackle some of the barriers to accessing family planning, but there are further areas which need development. Our cascade model of training, involves training Ugandan USHAPE trainers with the aim of future scale up and long-term development.

Teaching and research: challenges for academic staff

I enjoyed the recent Editorial in Pacific Conservation Biology by Mike Calver on the scholarship of teaching conservation biology (Calver 2015). The challenges faced by academic staff in universities who teach and undertake research are real. I agree with Calver (2015) that publishing papers on teaching initiatives provides opportunities for academics to contribute to the scholarship of teaching. Publishing papers about tertiary teaching can help academics to maintain their publication rate while engaging in teaching (see Tomcho et al. 2015). Publishing papers about teaching is only part of the solution to the challenges faced by academics who teach and do research. High, and sometimes unrealistic, expectations are placed on academic staff at universities who teach students and conduct research. Such staff are expected to have substantial research inputs (grants) and research outputs (papers), to provide high quality teaching to undergraduates and other coursework students, to supervise several post-graduate students, and to participate in administration and outreach. Calver’s (2015) point about promotion committees at universities valuing research productivity over teaching is valid. The expectations placed on academics who teach and do research are exacerbated by lack of understanding about levels of research productivity expected from different types of academic staff. While formal documents may specify different levels of research productivity required from research and teaching staff compared with research only staff, such differences are not emphasised in practice. Implicitly, if not explicitly, the research productivity (grants and papers) of teaching and research staff is often expected to be commensurate with that of research only staff. As one teaching and research academic said to me – the message to all academic staff from university management is write more papers (I would add – and publish them in highly cited journals, see Calver 2014 and references therein). Expecting similar levels of research productivity from teaching and research staff as from research only staff is unreasonable and unrealistic. The demand for unrealistic levels of research productivity from academic staff who teach and conduct research could be resolved by delineating categories of academic staff according to the allocations of their time to teaching and to research, and then defining and clearly communicating reasonable levels of research productivity expected from staff in the categories. The categories vary between universities, but broadly there are five groups of academic staff according to the breakdown of their time into teaching and research. The groups are: teaching only, teaching and research (relative time allocations from 50 : 50 to 30 : 70 either way), research only (post-doctoral fellows), research only (research and professorial fellows), research only (paid from contract funds, various titles of positions). Some research only staff give some lectures, but usually only for a few hours per semester. Defining and clearly communicating reasonable levels of research productivity expected from staff in the different groups would alleviate some of the tension caused by unrealistic demands on teaching and research academics for high research productivity. (Staff doing research on contract funds have other challenges in maintaining research outputs through papers, but this problem is outside the scope of this editorial.) The high and unrealistic expectations of research inputs and outputs from teaching and research academics exacerbate another problem. Graduates from undergraduate courses in environmental science in Australian universities mostly obtain positions in conservation and environmental management and policy. Few become scientists. Conservation and environmental managers and policy officers need a solid understanding of the science of their profession. Equally importantly, they need a strong understanding of the management and policy aspects of their profession, for example, working with stakeholders, communication skills, problem solving skills, managing projects and contractors, developing priorities, and legislation (see Thomas andNicita 2003,Muir and Schwartz 2009, Blickley et al. 2013, Rupp 2012). Such understanding is learnt best through tutorials using scenarios based on real world problems, as Calver (2015) briefly discusses. Perhaps Environmental Science courses should be called Environmental Science and Management, to reflect the professions for which they are training students. Academics who teach and are under pressure to have high research productivity struggle to find time to prepare tutorials that expose students to real world problems in environmental and conservation management and policy. Tutorials that provide scenarios about real world problems in conservation/ environmental management and policy are best run in conjunction with practitioners, that is, with people in relevant business, government and non-government organisations. Academics need to develop and maintain networks to know and interact with such people. Developing and maintaining such networks is time consuming. Academic staff who both teach and are expected to have high research productivity rarely have time to interact with conservation and environmental managers and CSIRO PUBLISHING

Territoriality: For and Against

This article will survey the main arguments for and against territoriality and conclude that it is the wrong way to go in the short run, but can perhaps be adopted in the medium to long run in conjunction with more fundamental international tax reform. The main reason that territoriality should not be adopted now is that the OECD may be about to recommend worldwide consolidation for all its members as part of the Base Erosion and Profit Shifting (BEPS) project, and if the OECD does that, all of the standard arguments in favor of territoriality and against abolishing deferral disappear.

Development of the BeefSpecs fat calculator to assist decision making to increase compliance rates with beef carcass specifications

The BeefSpecs fat calculator is a decision-support system developed to assist decision making on-farm to improve compliance rates with beef carcass specifications. BeefSpecs is underpinned by a research model run in conjunction with a translation process that converts inputs recorded in live animal and carcass assessment language into research model parameters. In contrast to many other research modelling systems, the changes in body composition predicted by the research model that underpins BeefSpecs are driven by growth rate. Use of this model removes the need for information concerning feed intake and dietary characteristics, which are impractical to collect on a routine basis in commercial production systems. A translation process was developed to use traits that are recorded routinely on-farm during normal production activities while allowing the original modelling system to run efficiently and accurately. This process aligns BeefSpecs with the language used by industry and increases the confidence of users in the underlying model theories. The outputs produced by BeefSpecs include final liveweight, final subcutaneous fat depth and hot standard carcass weight at the end of a specified feeding period. These traits contribute to the carcass specifications used to determine carcass value in the domestic and international markets supplied by the Australian beef industry, which directly aligns BeefSpecs with the decision-making styles of beef producers. During the development of BeefSpecs, potential users were consulted and enlisted in the evaluation process.

People seeking treatment for a new episode of neck pain typically have rapid improvement in symptoms: an observational study

What is the clinical course of a new episode of non-specific neck pain in people who are treated with multimodal physical therapies in a primary care setting? Observational study with 3-month follow-up, run in conjunction with a randomised trial. 181 adults who consulted a physiotherapist or chiropractor for a new episode of nonspecific neck pain. Time to recover from the episode of neck pain, time to recover normal activity, and pain and neck-related disability at three months. Clinical and demographic characteristics were investigated as potential predictors of recovery. Within 3 months, 53% of participants reported complete recovery from the episode of neck pain. On a scale from 0 (none) to 10 (worst), pain improved from 6.1 (SD 2.0) at baseline to 2.5 (SD 2.1) at 2 weeks and to 1.5 (SD 1.8) at 3 months. On a scale from 0 (none) to 50 (worst), disability improved from 15.5 (SD 7.4) at baseline to 5.4 (SD 6.4) at 3 months. Faster recovery was independently associated with better self-rated general health, shorter duration of symptoms, being a smoker, and absence of concomitant upper back pain or headache. Higher disability at 3 months was independently associated with higher disability at baseline, concomitant upper or lower back pain, older age, and previous sick leave for neck pain. People who seek physical treatments for a new episode of neck pain in this primary care setting typically have high pain scores that improve rapidly after commencing treatment. Although almost half of those who seek treatment do not recover completely within three months, residual pain and disability in this group is relatively low. Physiotherapists should reassure people with a new episode of neck pain that rapid improvement in symptoms is common, modifying this advice where applicable based on risk factors.

Proposals for a Revision of Kerberos When Run in Conjunction with the IPsec Protocol Suit

IPsec is an end to end secure communication protocol operating in the IP layer of the communications stack. It secures bilateral communication interchanges between hosts by encrypting individual IP packets. Kerberos provides a means of authenticating abstract entities to each other by via a trusted third party. It does this by encrypting packages, or tickets, of information using keys, which have been retained from previous exchanges. This investigation considers how Kerberos' internal message structures may be adapted when run in an IPsec environment, possibly avoiding layered encryptions, and encryptions whose purpose is to certify identity. 

Thought Exercises on Accountability and Performance Measures at the National Heart, Lung, and Blood Institute (NHLBI): An Invited Commentary for Circulation Research

Recently, popular magazines and newspapers broadcast skeptical headlines, such as, “Desperately Seeking Cures”1; “A Decade Later, Genetic Map Yields Few Cures”2; “Faltering Cancer Trials”3; and “Grant System Leads Cancer Researchers to Play It Safe.”4 Some patients, physicians, advocacy groups, journalists, scholars, and policymakers openly wonder about the value of billions of dollars in government-supported research. During the past 10 years, the NIH budget has doubled, yet cardiovascular disease, while decreasing in incidence and severity, is still the leading cause of death and cancer incidence and death rates have declined little. Along with “Where Are the Cures?” critics ask “Who Is Accountable?”5 There is a rapidly growing body of scholarship on the metrics of science, methods by which scientists, scientific organizations, policymakers, and funding agencies can gauge the value and impact of their work and investments.6 To assess the impact of the 2009 American Recovery and Reinvestment Act (ARRA), the National Science Foundation, the National Institutes of Health, and the White House Executive Office are engaged in an ambitious “STAR METRICS” project.7 Metrics often focus on publications and citations (“bibliometrics”) but also consider commercial products and quantitative impacts on practice or intellectual thought. Although scientists are typically eager to publish their work and see it cited, many worry about seeing their value to society, employers, and funders graded by black-box numbers.8 Some professional groups have harshly criticized bibliometrics, noting their inherent flaws and the risk that the act of measuring science will damage innovation, which is at the heart of the scientific enterprise.9 At NHLBI, we increasingly recognize that we need to be held accountable for our performance, which means that it is incumbent on us to assess the performance of the scientists and projects we choose to support. …

My School Rocks! Dancing Disney's High School Musical in India

High School Musical, the 2006 Disney Channel original movie, was a surprise hit in the United States, but its Bollywood-style format and sanitized depiction of American high school life contributed to its popularity in India as well. The Disney Channel, which entered the growing Indian market for children's television in 2004, has been a leader in developing strategies for localization. Many standard strategies are visible in the marketing of High School Musical, including dubbing content into local languages, creating content locally or drawing on local themes, and running local promotions and competitions. The My School Rocks dance competition, run in conjunction with the release of High School Musical, added creative and performance components to the equation that encouraged Indian kids to actively alter and interpret the film's musical numbers, thus making them relevant to their particular cultural experiences. Additionally, My School Rocks took advantage of the film's musical format to exploit similarities with the popular existing Bollywood industry, by both imitating popular performance practices inspired by Bollywood song-and-dance sequences and enlisting well-known Bollywood choreographers to serve as judges. The promotion involved schools, through the existing structure of interschool dance competitions, and local communities, through the voting that took place on the Disney India website. Through this Asia-specific competition, Disney encouraged children to take ownership of the film's content by creating and performing original dances to the songs, thus developing hybrid and bilingual choreographies that function as signifiers of class-based urban Indian cosmopolitanism.

Darden's Luckiest Student 2008

The case describes a three-factor, full-factorial experiment run in conjunction with the Darden's Luckiest Student event of 2008. Prior to identifying Darden's Luckiest, all 300 first-year students made binding decisions between varying amounts of cash and the opportunity to select one of two identical briefcases. One briefcase contained $18,750; the other contained $0. Students are asked to analyze the results of the experiment and draw conclusions with respect to how the experimental factors influenced student decisions.

Skin Friction Measurements Using Oil-Film Interferometry in NASA's 11-Foot Transonic Wind Tunnel

Skin-friction measurements were obtained on two laminar flow airfoils in the NASA Ames 11-ft transonic wind tunnel using oil-film interferometry. Improvements in the experimental technique allowed skin-friction measurements at two conditions per run in conjunction with performance testing, thus reducing the impact on the run schedule. Quantitative measurements of skin friction were used to determine transition location and the extent of separation (if any) on the airfoils providing much more insight into the flow than flow viz. The technique has been extended to obtain a quantitative measure of shear in the reversed flow region. The effects of various disturbances to the boundary layer were also investigated. Laminar flow was found as far back as 60% chord at a Reynolds number of 4.5 x 10 6 .

The impact of downward social information on contribution decisions

In this paper we study the effect of downward social information in contribution decisions to fund public goods. We describe the results of a field experiment run in conjunction with the fundraising campaigns of a public radio station. Renewing members are presented with social information (information about another donor’s contribution) which is either above or below their previous (last year’s) contribution. We find that respondents change their contribution in the direction of the social information; increasing their contribution when the social information is above their previous contribution, and decreasing their contribution when the social information is below. We hypothesize about the psychological motivations that may cause the results and test these hypotheses by comparing the relative size of the upward and downward shifts. These results improve our understanding of cooperation in public good provision and suggest differential costs and benefits to fundraisers in providing social information.

Four years of the EPSRC SRS Service

SinceOctober 2001, the EPSRCnational crystallography service in the UK has had a SRS component, run in conjunction with the national crystallographic service based at Southampton University, through the use of station 9.8 at Daresbury laboratory. Over the course of the past 3.5 years regular monthly visits have taken place, and a total of 385 data collections made, averaging 6 data collections per day of beam time. This poster reports the many successes of the service, and includes statistics on users and publications benefiting from the service. The reader will hopefully gain an insight into a service utilizing the most successful small molecule synchrotron beam line in the world. m41.p20

Argumentation in AI and Law: Editors' Introduction

1. Overview Argument is central to law: legal disputes arise out of a disagreement between two parties and, since the disappearance of trials by ordeal and combat, such disputes are resolved by the parties to the dispute presenting arguments for their position to an agreed arbiter, who will typically justify the choice of the arguments he accepts with an argument of his own, intended to convince superior courts and the public at large. Given the centrality of argument to law, it is unsurprising that AI systems intended to model legal reasoning have found it necessary to model argument. This volume contains a collection of papers representing some of the very latest work on argumentation in AI and Law. The papers derive from a workshop run in conjunction with the Tenth International Conference on AI and Law, held in Bologna in June 2005. The papers have since been significantly extended and revised for publication here. In this introduction we will try to provide some of the context in which this work was done. We will not pretend to give a complete survey, but rather to introduce the key concerns and issues relating to argumentation which have arisen in previous work in AI and Law. Major topics which have emerged as important in AI and Law and argumentation include: – Arguing on the basis of precedent cases – Using argumentation to resolve rule conflicts and explore defeasibility – Dialogue and dialectics – Argument Schemes – Determining whether an attack on an argument is successful We will briefly consider each of these in turn.

Sandvika, Norway: Spesialsykehuset for Epilepsi HF: The National Centre for Epilepsy at Sandvika, Norway

Sandvika, Norway: Spesialsykehuset for Epilepsi HF: The National Centre for Epilepsy at Sandvika, Norway

Health on the streets. Interview by Dina Leifer.

A clinic for homeless people run in conjunction with the big issue is proving to be a great success. dina leifer reports