Increased levels of RNA oxidation enhance the reversion frequency in aging pro-apoptotic yeast mutants

Despite recent advances in understanding the complexity of RNA processes, regulation of the metabolism of oxidized cellular RNAs and the mechanisms through which oxidized ribonucleotides affect mRNA translation, and consequently cell viability, are not well characterized. We show here that the level of oxidized RNAs is markedly increased in a yeast decapping Kllsm4Δ1 mutant, which accumulates mRNAs, ages much faster that the wild type strain and undergoes regulated-cell-death. We also found that in Kllsm4Δ1 cells the mutation rate increases during chronological life span indicating that the capacity to han- dle oxidized RNAs in yeast declines with aging. Lowering intracellular ROS levels by antioxidants recovers the wild- type phenotype of mutant cells, including reduced amount of oxidized RNAs and lower mutation rate. Since mRNA oxidation was reported to occur in different neurodegen- erative diseases, decapping-deficient cells may represent a useful tool for deciphering molecular mechanisms of cell response to such conditions, providing new insights into RNA modification-based pathogenesis

RNA secondary structure prediction from multi-aligned sequences

It has been well accepted that the RNA secondary structures of most functional non-coding RNAs (ncRNAs) are closely related to their functions and are conserved during evolution. Hence, prediction of conserved secondary structures from evolutionarily related sequences is one important task in RNA bioinformatics; the methods are useful not only to further functional analyses of ncRNAs but also to improve the accuracy of secondary structure predictions and to find novel functional RNAs from the genome. In this review, I focus on common secondary structure prediction from a given aligned RNA sequence, in which one secondary structure whose length is equal to that of the input alignment is predicted. I systematically review and classify existing tools and algorithms for the problem, by utilizing the information employed in the tools and by adopting a unified viewpoint based on maximum expected gain (MEG) estimators. I believe that this classification will allow a deeper understanding of each tool and provide users with useful information for selecting tools for common secondary structure predictions.Comment: A preprint of an invited review manuscript that will be published in a chapter of the book `Methods in Molecular Biology'. Note that this version of the manuscript may differ from the published versio

High School Exit Examinations: When Do Learning Effects Generalize?

This paper reviews international and domestic evidence on the effects of three types of high school exit exam systems: voluntary curriculum-based external exit exams, universal curriculum-based external exit exam systems and minimum competency tests that must be passed to receive a regular high school diploma. The nations and provinces that use Universal CBEEES (and typically teacher grades as well) to signal student achievement have significantly higher achievement levels and smaller differentials by family background than otherwise comparable jurisdictions that base high stakes decisions on voluntary college admissions tests and/or teacher grades. The introduction of Universal CBEEES in New York and North Carolina during the 1990s was associated with large increases in math achievement on NAEP tests. Research on MCTs and high school accountability tests is less conclusive because these systems are new and have only been implemented in one country. Cross-section studies using a comprehensive set of controls for family background have not found that students in MCT states score higher on audit tests like the NAEP that carry no stakes for the test taker. The analysis reported in table 1 tells us that the five states that introduced MCTs during the 1990s had significantly larger improvements on NAEP tests than states that made no change in their student accountability regime. The gains, however, are smaller than for the states introducing Universal CBEEES. New York and North Carolina. The most positive finding about MCTs is that students in MCT states earn significantly more during the first eight years after graduation than comparable students in other states suggesting that MCTs improve employer perceptions of the quality of the recent graduates of local high schools

Gravitational Radiation from Post-Newtonian Sources and Inspiralling Compact Binaries

The article reviews the current status of a theoretical approach to the problem of the emission of gravitational waves by isolated systems in the context of general relativity. Part A of the article deals with general post-Newtonian sources. The exterior field of the source is investigated by means of a combination of analytic post-Minkowskian and multipolar approximations. The physical observables in the far-zone of the source are described by a specific set of radiative multipole moments. By matching the exterior solution to the metric of the post-Newtonian source in the near-zone we obtain the explicit expressions of the source multipole moments. The relationships between the radiative and source moments involve many non-linear multipole interactions, among them those associated with the tails (and tails-of-tails) of gravitational waves. Part B of the article is devoted to the application to compact binary systems. We present the equations of binary motion, and the associated Lagrangian and Hamiltonian, at the third post-Newtonian (3PN) order beyond the Newtonian acceleration. The gravitational-wave energy flux, taking consistently into account the relativistic corrections in the binary moments as well as the various tail effects, is derived through 3.5PN order with respect to the quadrupole formalism. The binary's orbital phase, whose prior knowledge is crucial for searching and analyzing the signals from inspiralling compact binaries, is deduced from an energy balance argument.Comment: 109 pages, 1 figure; this version is an update of the Living Review article originally published in 2002; available on-line at http://www.livingreviews.org

Assessing Graphical Robot Aids for Interactive Co-working

The shift towards more collaborative working between humans and robots increases the need for improved interfaces. Alongside robust measures to ensure safety and task performance, humans need to gain the confidence in robot co-operators to enable true collaboration. This research investigates how graphical signage can support human–robot co-working, with the intention of increased productivity. Participants are required to co-work with a KUKA iiwa lightweight manipulator on a manufacturing task. The three conditions in the experiment differ in the signage presented to the participants – signage relevant to the task, irrelevant to the task, or no signage. A change between three conditions is expected in anxiety and negative attitudes towards robots; error rate; response time; and participants’ complacency, suggested by facial expressions. In addition to understanding how graphical languages can support human–robot co-working, this study provides a basis for further collaborative research to explore human–robot co-working in more detail

The use of Reamer–irrigator–aspirator in the management of long bone osteomyelitis: an update

Purpose: Reamer–irrigator–aspirator (RIA) is an innovative device that its indications have recently been expanded to the management of long bone infections. Methods: In this narrative review, we summarise the most important studies in the field and we present the current open questions pertaining to the use of RIA in the management of osteomyelitis of long bones. Results: The relevant literature is sparse and low quality. Nevertheless, the use of RIA for infected cases has yielded promising outcomes in specialised centres. Technical aspects that merit special attention in osteomyelitis of long bones are its inapplicability in small diameter long bones, the inadequate debridement of wide metaphyseal areas and the potential bleeding sequelae. The use of RIA in open fracture management to reduce infection risk has not gained acceptance. The antibiotic impregnated nails and rods constitute a complimentary strategy for the management of infections. Conclusions: The use of RIA for the management of long bone infections is an innovative and promising strategy. High quality studies are needed to shed light in its efficacy compared to conventional methods of management of osteomyelitis of long bones

Genomic prediction in CIMMYT maize and wheat breeding programs

Genomic selection (GS) has been implemented in animal and plant species, and is regarded as a useful tool for accelerating genetic gains. Varying levels of genomic prediction accuracy have been obtained in plants, depending on the prediction problem assessed and on several other factors, such as trait heritability, the relationship between the individuals to be predicted and those used to train the models for prediction, number of markers, sample size and genotype × environment interaction (GE). The main objective of this article is to describe the results of genomic prediction in International Maize and Wheat Improvement Center's (CIMMYT's) maize and wheat breeding programs, from the initial assessment of the predictive ability of different models using pedigree and marker information to the present, when methods for implementing GS in practical global maize and wheat breeding programs are being studied and investigated. Results show that pedigree (population structure) accounts for a sizeable proportion of the prediction accuracy when a global population is the prediction problem to be assessed. However, when the prediction uses unrelated populations to train the prediction equations, prediction accuracy becomes negligible. When genomic prediction includes modeling GE, an increase in prediction accuracy can be achieved by borrowing information from correlated environments. Several questions on how to incorporate GS into CIMMYT's maize and wheat programs remain unanswered and subject to further investigation, for example, prediction within and between related bi-parental crosses. Further research on the quantification of breeding value components for GS in plant breeding populations is required.J Crossa, P Pérez, J Hickey, J Burgueño, L Ornella, J Cerón-Rojas, X Zhang, S Dreisigacker, R Babu, Y Li, D Bonnett and K Mathew

Regulators of genetic risk of breast cancer identified by integrative network analysis.

Genetic risk for breast cancer is conferred by a combination of multiple variants of small effect. To better understand how risk loci might combine, we examined whether risk-associated genes share regulatory mechanisms. We created a breast cancer gene regulatory network comprising transcription factors and groups of putative target genes (regulons) and asked whether specific regulons are enriched for genes associated with risk loci via expression quantitative trait loci (eQTLs). We identified 36 overlapping regulons that were enriched for risk loci and formed a distinct cluster within the network, suggesting shared biology. The risk transcription factors driving these regulons are frequently mutated in cancer and lie in two opposing subgroups, which relate to estrogen receptor (ER)(+) luminal A or luminal B and ER(-) basal-like cancers and to different luminal epithelial cell populations in the adult mammary gland. Our network approach provides a foundation for determining the regulatory circuits governing breast cancer, to identify targets for intervention, and is transferable to other disease settings.This work was funded by Cancer Research UK and the Breast Cancer Research Foundation. MAAC is funded by the National Research Council (CNPq) of Brazil. TEH held a fellowship from the US DOD Breast Cancer Research Program (W81XWH-11-1-0592) and is currently supported by an RAH Career Development Fellowship (Australia). TEH and WDT are funded by the NHMRC of Australia (NHMRC) (ID: 1008349 WDT; 1084416 WDT, TEH) and Cancer Australia/National Breast Cancer Foundation (ID 627229; WDT, TEH). BAJP is a Gibb Fellow of Cancer Research UK. We would like to acknowledge the support of The University of Cambridge, Cancer Research UK and Hutchison Whampoa Limited.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.345

A Three-Year Study on Peer Evaluation in a Software Engineering Project Course

Background: Peer evaluation in software engineering (SE) project courses enhances the learning experience of students. It also helps instructors monitor and assess both teams and individual students. Peer evaluations might influence the way individual students and teams work therefore the quality of the peer evaluations should be tracked through the project course. Contribution: In this paper, we analyzed the quality and scoring behavior of students in peer evaluation in an undergraduate SE project course over three years. Research Questions: RQ1: What is the quality of peer evaluation of undergraduate students in a SE project course? RQ2: How do undergraduate students in a SE project course score each other? Methodology: The quality of peer evaluation (length, level of detail, etc.) and scoring of peers based on various aspects of peer evaluations of third-year students in a year-long SE project course were studied. Taking into account the grade students received at the end of the course (A, B, C and F-calibers), peer evaluations were categorized, analyzed over time and compared between students calibers. Findings: After analyzing 6,854 peer evaluations from 193 students, it was found that the quality of peer evaluations across students was mostly consistent throughout the course. Also, it was observed that quantitative aspects of the peer evaluation were scored similarly across student calibers. However, the qualitative aspects of the peer evaluation were impacted by the caliber of students. These findings suggest that weaker students (i.e., C-caliber students) generally receive better quality peer evaluations than stronger students (i.e., A-caliber students). Lastly, a preliminary analysis showed a positive connotation of emotions and sentiments found in textual feedback delivered by students