bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR2: Functional characterization of p53-regulated long intervening non-coding RNAs (lincRNAs
Authors: Dimitrova Nadya M. , Jacks Tyler 
Published: April 2013

Abstract
LincRNAs (long intervening noncoding RNAs) constitute a novel class of long, noncoding RNAs that have been implicated in regulating gene expression in diverse biological processes by modulating the activity of chromatin-modifying complexes. In collaboration with the Rinn laboratory at the Broad Institute, we have identified a set of lincRNAs that appear to be direct transcriptional targets of p53. These lincRNAs contain p53 binding elements in their promoter regions and are strongly upregulated in a p53-dependent manner upon DNA damage and in response to oncogenic stress. We have hypothesized that these lincRNAs may be new components of the p53 network and may contribute to p53 tumor suppressor function by regulating the expression of genes in cancer-relevant pathways. Using a combination of molecular genetic studies, cell biology, biochemistry, as well as gene targeting in the mouse, our aim is to dissect the biological function of these lincRNAs in vivo and in isolated cells.
To date, we have generated a conditional knockout mutant for lincRNA-p21, one of the p53-regulated lincRNAs, which was recently shown to mediate gene repression in the p53 transcriptional network. Using this genetic tool, we plan to characterize the consequences of lincRNA-p21 loss in mice and in isolated mouse embryonic fibroblasts. Our goal is to identify genes that are regulated by lincRNA-p21 and to map out interactions between lincRNA-p21 and the p53 transcriptional network. We will also focus on dissecting the mechanism by which lincRNA-p21 may regulate the expression of target genes.
We have also identified a lincRNA, linc9, which is induced by DNA damage in a dose-dependent manner. Even though the expression of linc9 appears to be p53-independent, our preliminary experiments indicate that linc9 may influence the outcome of p53 activation by promoting apoptosis in response to high levels of DNA damage.
In sum, by studying the function and mechanism of p53-regulated and DNA damage-induced lincRNAs, we hope to achieve a better understanding of the role of long noncoding RNAs in modulating the p53 pathway and more broadly in regulating cancer-related processes.
This abstract is also presented as Poster B19.
Citation Format: Nadya M. Dimitrova, Tyler Jacks. Functional characterization of p53-regulated long intervening non-coding RNAs (lincRNAs) [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr PR2.
The Basic Principles of Chimeric Antigen Receptor Design
Authors: Sadelain Michel , Brentjens Renier , Rivière Isabelle 
Published: April 2013

AbstractChimeric antigen receptors (CAR) are recombinant receptors that provide both antigen-binding and T-cell–activating functions. A multitude of CARs has been reported over the past decade, targeting an array of cell surface tumor antigens. Their biologic functions have dramatically changed following the introduction of tripartite receptors comprising a costimulatory domain, termed second-generation CARs. These have recently shown clinical benefit in patients treated with CD19-targeted autologous T cells. CARs may be combined with costimulatory ligands, chimeric costimulatory receptors, or cytokines to further enhance T-cell potency, specificity, and safety. CARs represent a new class of drugs with exciting potential for cancer immunotherapy.Significance: CARs are a new class of drugs with great potential for cancer immunotherapy. Upon their expression in T lymphocytes, CARs direct potent, targeted immune responses that have recently shown encouraging clinical outcomes in a subset of patients with B-cell malignancies. This review focuses on the design of CARs, including the requirements for optimal antigen recognition and different modalities to provide costimulatory support to targeted T cells, which include the use of second- and third-generation CARs, costimulatory ligands, chimeric costimulatory receptors, and cytokines. Cancer Discov; 3(4); 388–98. ©2013 AACR.
T1 Measurements Identify Extracellular Volume Expansion in Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers With and Without Left Ventricular Hypertrophy
Authors: Ho Carolyn Y. , Abbasi Siddique A. , Neilan Tomas G. , Shah Ravi V. , Chen Yucheng , Heydari Bobak , Cirino Allison L. , Lakdawala Neal K. , Orav E. John , González Arantxa , López Begoña , Díez Javier , Jerosch-Herold Michael , Kwong Raymond Y. 
Published: April 2013

Background—
Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy (HCM) and a potential substrate for arrhythmias and heart failure. Sarcomere mutations seem to induce profibrotic changes before left ventricular hypertrophy (LVH) develops. To further evaluate these processes, we used cardiac magnetic resonance with T1 measurements on a genotyped HCM population to quantify myocardial extracellular volume (ECV).

Methods and Results—

Sarcomere mutation carriers with LVH (G+/LVH+, n=37) and without LVH (G+/LVH−, n=29), patients with HCM without mutations (sarcomere-negative HCM, n=11), and healthy controls (n=11) underwent contrast cardiac magnetic resonance, measuring T1 times pre- and postgadolinium infusion. Concurrent echocardiography and serum biomarkers of collagen synthesis, hemodynamic stress, and myocardial injury were also available in a subset. Compared with controls, ECV was increased in patients with overt HCM, as well as G+/LVH− mutation carriers (ECV=0.36±0.01, 0.33±0.01, 0.27±0.01 in G+/LVH+, G+/LVH−, controls, respectively;
P
≤0.001 for all comparisons). ECV correlated with N-terminal probrain natriuretic peptide levels (r=0.58;
P
<0.001) and global E’ velocity (r=−0.48;
P
<0.001). Late gadolinium enhancement was present in >60% of overt patients with HCM but absent from G+/LVH− subjects. Both ECV and late gadolinium enhancement were more extensive in sarcomeric HCM than sarcomere-negative HCM.

Conclusions—
Myocardial ECV is increased in HCM sarcomere mutation carriers even in the absence of LVH. These data provide additional support that fibrotic remodeling is triggered early in disease pathogenesis. Quantifying ECV may help characterize the development of myocardial fibrosis in HCM and ultimately assist in developing novel disease-modifying therapy, targeting interstitial fibrosis.
In-Situ Oxygen Analyser for Pressurised Combustor
Authors: Horton J. L. , Perez J. , Sanders J. Sadler , Stewart J. , Rogers M. 
Published: April 2013

Due to the increasingly stringent environmental regulations placed on the power generation industry, new methods of generating power utilising the abundant availability of coal are being developed. Included in this development is the Power Systems Development Facility's (PSDF) processes of applying pressurised combustion and gasification to increase efficiency while eliminating many of the environmentally unfriendly emissions. As with any combustion process, the measurement of oxygen in the flue gas is vitally important. The availability of the zirconium oxide in-situ oxygen analyser several years ago was a welcome change to those who had tried to maintain a real-time, accurate flue gas oxygen measurement. The zirconium oxide in-situ oxygen analyser is now the chosen method for measuring flue gas oxygen at virtually all power boiler outlets. During the detail design stages of the PSDF in the early 1990s, an in-situ oxygen analyser could not be found that would operate at the required combustor pressures of 150–300 psig. Recently, following numerous inquiries of various vendors around the world, a vendor was found who has developed a sensor that will act as a pressure boundary to 170 psig and an electronics unit that will accept a 4–20 mA input from a pressure transmitter for oxygen partial pressure compensation. This analyser has been successfully tested in the combustor outlet of the PSDF at a process pressure of 130 psig. The performance of the analyser is presented.
Air Traffic Surveillance — Building Capacity and Enhancing Safety
Authors: Rose Andrew 
Published: April 2013

Surveillance of aircraft is a key requirement of any effective air traffic control system. Classical methods of surveillance, both ground-to-air and air-to-air, have their limitations depending upon the environment in which they are used. These limitations primarily manifest themselves in terms of cost and capacity, with surveillance capability already being a limiting factor in the growth of air traffic in certain regions. Various methods and applications are being developed to overcome surveillance limitations on air traffic growth, the primary objective of which is to enable increased traffic flows whilst enhancing the existing levels of safety. Developments underway in various regions of the world are considering both near-term and longer-term enhancements to surveillance capability as part of a more effective air traffic management system. One prime focus of these developments is a shift away from classical ‘active’ surveillance to a ‘passive’ surveillance based system where the aircraft is responsible for providing the necessary surveillance data rather than the interrogating system. Such an approach can provide significant enhancements in terms of cost and capacity but also brings potential safety risks that need to be effectively managed, particularly during the transition. The objective of this paper is to outline the benefits that such a transition could provide whilst highlighting some of the key safety issues and how they could be addressed. The paper concludes with a vision of a future air traffic surveillance system and a safe transition towards it.
Where on Earth Am I?: Global Navigation Satellite Systems
Authors: Cornwall M G , Lewes  , Sussex E 
Published: April 2013

Measuring your absolute global position to within a few centimetres or relative changes in position anywhere on Earth to within a millimetre or so, seemed impossible just a decade or so ago. The Global Positioning System (GPS) has made this not just possible but routine. In addition everyone is familiar with the fact that ‘Satnavs’ will guide you with uncanny accuracy to any selected destination. How does GPS achieve such precision? This short review will explain the basic geometrical principles, the practical implementation and some of the burgeoning applications of GPS. But first a word about nomenclature. Although the ‘GPS’ is often used to describe the satellite based global location system, there are in fact several other systems in development which provide or will provide equal or even enhanced precision within the next few years. The generic description for these is Global Navigation Satellite Systems (GNSS), but like ‘Hoover’ and ‘Biro’, ‘GPS’ has become the generic acronym often casually used to refer to the overall system. Throughout this article the information and examples refer to the GPS. More about the proliferating rivals to GPS later.
Quality Standards and Regulation: Challenges for Digital Forensics
Authors: Marshall Angus M. 
Published: April 2013

Concern over the quality of science and scientists has led to a number of recommendations from the judiciary and government bodies. The Forensic Science Regulator, appointed within the Home Office, has produced a draft Code of Practice for Forensic Science Providers to the criminal justice system (CJS) with accompanying annexes for guidance in specific disciplines. All Forensic Science Providers (FSPs) are required to comply with the code of practice by 2013. The annex for digital evidence adopts existing principles of good practice and extends them to include a requirement for demonstration of fitness for purpose in the context of the CJS. The industry, however, has identified that a proper definition of purpose is likely to be quite complex and must embark on a programme of research in order to fully define this before fitness can be demonstrated.
ACL Reconstruction in Patients Aged 40 Years and Older
Authors: Brown Christopher A. , McAdams Timothy R. , Harris Alex H.S. , Maffulli Nicola , Safran Marc R. 
Published: April 2013

Background: Treatment of the anterior cruciate ligament (ACL)–deficient knee in older patients remains a core debate. Purpose: To perform a systematic review of studies that assessed outcomes in patients aged 40 years and older treated with ACL reconstruction and to provide a new methodological scoring system that is directed at critical assessment of studies evaluating ACL surgical outcomes: the ACL Methodology Score (AMS). Study Design: Systematic review. Methods: A comprehensive literature search was performed from 1995 to 2012 using MEDLINE, EMBASE, and Scopus. Inclusion criteria for studies were primary ACL injury, patient age of 40 years and older, and mean follow-up of at least 21 months after reconstruction. Nineteen studies met the inclusion criteria from the 371 abstracts from MEDLINE and 880 abstracts from Scopus. Clinical outcomes (International Knee Documentation Committee [IKDC], Lysholm, and Tegner activity scores), joint stability measures (Lachman test, pivot-shift test, and instrumented knee arthrometer assessment), graft type, complications, and reported chondral or meniscal injury were evaluated in this review. A new methodology scoring system was developed to be specific at critically analyzing ACL outcome studies and used to examine each study design. Results: Nineteen studies describing 627 patients (632 knees; mean age, 49.0 years; range, 42.6-60.0 years) were included in the review. The mean time to surgery was 32.0 months (range, 2.9-88.0 months), with a mean follow-up of 40.2 months (range, 21.0-114.0 months). The IKDC, Lysholm, and Tegner scores and knee laxity assessment indicated favorable results in the studies that reported these outcomes. Patients did not demonstrate a significant difference between graft types and functional outcome scores or stability assessment. The mean AMS was 43.9 ± 7.2 (range, 33.5-57.5). The level of evidence rating did not positively correlate with the AMS, which suggests that the new AMS system may be able to detect errors in methodology or reporting that may not be taken into account by the classic level of evidence rating. Conclusion: Patients aged 40 years and older with an ACL injury can have satisfactory outcomes after reconstruction. However, the quality of currently available data is still limited, such that further well-designed studies are needed to determine long-term efficacy and to better inform our patients with regard to expected outcomes.
Ulnar Collateral Ligament Reconstruction Using Bisuspensory Fixation
Authors: Jackson Timothy J. , Adamson Gregory J. , Peterson Alexander , Patton John , McGarry Michelle H. , Lee Thay Q. 
Published: April 2013

Background: Many ulnar collateral ligament (UCL) reconstruction techniques have been created and biomechanically tested. Single-bundle reconstructions aim to re-create the important anterior bundle of the UCL. To date, no technique has utilized suspensory fixation on the ulnar and humeral sides to create a single-bundle reconstruction. Hypothesis: The bisuspensory technique will restore valgus laxity to its native state, with comparable load-to-failure characteristics to the docking technique. Study Design: Controlled laboratory study. Methods: Six matched pairs of fresh-frozen cadaveric elbows were randomized to undergo UCL reconstruction using either the docking technique or a novel single-bundle bisuspensory technique. Valgus laxity and rotation measurements were quantified using a MicroScribe 3DLX digitizer at various flexion angles for the native ligament, transected ligament, and 1 of the 2 tested reconstructed ligaments. Laxity testing was performed from maximum extension to 120° of flexion. Each reconstruction was then tested to failure, and the method of failure was recorded. Results: Valgus laxity was restored to the intact state at all degrees of elbow flexion for both the docking and bisuspensory techniques. In load-to-failure testing, there was no significant difference with regard to stiffness, ultimate torque, ultimate torque angle, energy absorbed, and applied moment to reach 10° of valgus. Yield torques for the bisuspensory and docking reconstructions were 18.7 ± 7.8 N·m and 18.6 ± 4.4 N·m, respectively ( P = .95). The ultimate torque for the bisuspensory technique measured 26.5 ± 9.2 N·m and for the docking technique measured 25.1 ± 7.1 N·m ( P = .78). Conclusion: The bisuspensory fixation technique, a reproducible single-bundle reconstruction, was able to restore valgus laxity to the native state, with similar load-to-failure characteristics as the docking technique. Clinical Relevance: This reconstruction technique could be considered in a clinical setting as a primary method of UCL reconstruction or as a backup fixation method should intraoperative complications occur.
Patrick de Maré’s Median Group and Its Application to Prison and the Community
Authors: Parsons David 
Published: April 2013

This presentation to the Bolzano Congress in 2010 describes the value of Median Group Dialogue in work with offenders in prison and the community, and the success achieved. Pat de Maré’s Median Group is the missing link between the disaffected individual and the depersonalized institution, which can bring about a transformation of humanizing the institution and socializing the individual. Institutional failure has resulted in a chasm between an increasingly sophisticated/divided society fuelled by the rapid advance of the technological revolution and the outmoded feudal controlling institution. When free to operate effectively the Median Group creates an atmosphere where the institution can become flexible and sensitive towards the needs and demands of individual members. Having illustrated the application of Median Group Dialogue to the prison situation, this article proceeds to the difficulties encountered through the tendency of ossified institutions to reject change, and imagines another way forward starting in the community at large.
“It Helps Me Transform in My Life From the Past to the New”
Authors: Vindevogel Sofie , Broekaert Eric , Derluyn Ilse 
Published: April 2013

Although former child soldiers face considerable challenges after their return from the warring faction to the war-affected society, the presence of resources enables many to maintain well-being in the wake of child soldiering. Academic research has recently engaged with identifying these salient resources, but has left the question why they are helpful to former child soldiers largely unaddressed. This study therefore focuses on the meaning underlying certain phenomena that causes them to become resources. Semistructured in-depth interviews and a free-listing task on resources were conducted with 48 northern Ugandan former child soldiers. The phenomenological hermeneutical method is applied to analyze their lived experiences and the meaning they assign to resources. Four essential themes emerge from this study, representing the fourfold meaning of resources for former child soldiers in helping them (a) to break with their former existence as child soldiers, (b) to be able to overcome the challenges in their current life, (c) to belong to others and the environment to which they have returned, and (d) to become the person they aspire to be. Considering these research themes in the context of former child soldiers’ return process, parallels with theories on transition are recognized and further explored so as to contextualize this emerging meaning. As such, this research delivers empirical evidence illustrating how resources help to pilot former child soldiers through transition in the wake of child soldiering.
Spanish LupusPRO: cross-cultural validation study for lupus
Authors: Jolly M , Toloza S , Block J , Mikolaitis R , Kosinski M , Wallace D , Durran-Barragan S , Bertoli A , Blazevic I , Vilá L , Cooray D , Moldovan I , Katsaros E , Weisman M , Torralba KM , Alarcón G 
Published: April 2013

Purpose LupusPRO is a disease-targeted, patient-reported, outcome measure that was developed and validated among US patients with systemic lupus erythematosus (SLE). To expand the availability and use of the tool, we undertook a cross-cultural adaptation and validation study of the Spanish-translated version of the LupusPRO. Method Forward and back translations of the 43-item English LupusPRO were undertaken and pretested in five individuals. The finalized Spanish version was administered to 211 SLE patients of Hispanic ancestry from the US and Latin America. Short Form-36 (Spanish) and Spanish LupusPRO were also administered. Disease activity was ascertained using the systemic lupus erythematosus disease activity index. A Spanish LupusPRO questionnaire that could be completed within 2–3 days was mailed to SLE patients of Hispanic ancestry and they mailed it back. Internal consistency reliability, test-retest reliability, criterion validity (against disease activity or health status) and convergent validity were tested. All reported p values are two-tailed. Results A total of 211 Spanish-speaking SLE patients (90% women) participated. Test-retest reliability of LupusPRO domains ranged from 0.80–0.95, while internal consistency reliability of the domains ranged from 0.71–0.96. Convergent validity with corresponding domains of the SF-36 was present. All health-related quality of life domains of the LupusPRO (except procreation) performed well against disease activity measures, establishing its criterion validity. Confirmatory factor analysis showed a good fit. Conclusion The Spanish LupusPRO has fair psychometric properties and is now available to be included in clinical trials and in longitudinal studies for testing of responsiveness to change.
Circulating microRNAs in hematological diseases: principles, challenges, and perspectives
Authors: Grasedieck Sarah , Sorrentino Antonio , Langer Christian , Buske Christian , Döhner Hartmut , Mertens Daniel , Kuchenbauer Florian 
Published: April 2013

AbstractThe complex microRNA (miRNA) network plays an important role in the regulation of cellular processes such as development, differentiation, and apoptosis. Recently, the presence of cell-free miRNAs that circulate in body fluids was discovered. The ability of these circulating miRNAs to mirror physiological and pathophysiological conditions as well as their high stability in stored patient samples underlines the potential of these molecules to serve as biomarkers for various diseases. In this review, we describe recent findings in miRNA-mediated cell-to-cell communication and the functions of circulating miRNAs in the field of hematology. Furthermore, we discuss current approaches to design biomarker studies with circulating miRNAs. This article critically reviews the novel field of circulating miRNAs and highlights their suitability for clinical and basic research in addition to their potential as a novel class of biomarkers.