Run Generation Revisited: What Goes Up May or May Not Come Down

In this paper, we revisit the classic problem of run generation. Run generation is the first phase of external-memory sorting, where the objective is to scan through the data, reorder elements using a small buffer of size M , and output runs (contiguously sorted chunks of elements) that are as long as possible. We develop algorithms for minimizing the total number of runs (or equivalently, maximizing the average run length) when the runs are allowed to be sorted or reverse sorted. We study the problem in the online setting, both with and without resource augmentation, and in the offline setting. (1) We analyze alternating-up-down replacement selection (runs alternate between sorted and reverse sorted), which was studied by Knuth as far back as 1963. We show that this simple policy is asymptotically optimal. Specifically, we show that alternating-up-down replacement selection is 2-competitive and no deterministic online algorithm can perform better. (2) We give online algorithms having smaller competitive ratios with resource augmentation. Specifically, we exhibit a deterministic algorithm that, when given a buffer of size 4M , is able to match or beat any optimal algorithm having a buffer of size M . Furthermore, we present a randomized online algorithm which is 7/4-competitive when given a buffer twice that of the optimal. (3) We demonstrate that performance can also be improved with a small amount of foresight. We give an algorithm, which is 3/2-competitive, with foreknowledge of the next 3M elements of the input stream. For the extreme case where all future elements are known, we design a PTAS for computing the optimal strategy a run generation algorithm must follow. (4) Finally, we present algorithms tailored for nearly sorted inputs which are guaranteed to have optimal solutions with sufficiently long runs

Telomeric RNAs are essential to maintain telomeres

Telomeres are transcribed generating long non-coding RNAs known as TERRA. Deciphering the role of TERRA has been one of the unsolved issues of telomere biology in the past decade. This has been, in part, due to lack of knowledge on the TERRA loci, thus preventing functional genetic studies. Here, we describe that long non-coding RNAs with TERRA features are transcribed from the human 20q and Xp subtelomeres. Deletion of the 20q locus by using the CRISPR-Cas9 technology causes a dramatic decrease in TERRA levels, while deletion of the Xp locus does not result in decreased TERRA levels. Strikingly, 20q-TERRA ablation leads to dramatic loss of telomere sequences and the induction of a massive DNA damage response. These findings identify chromosome 20q as a main TERRA locus in human cells and represent the first demonstration in any organism of the essential role of TERRA in the maintenance of telomeres.We are indebted to R. Torres and S. Rodriguez for advice in the CRISPR-Cas9 technology and helpful discussions. We thank D. Megías for the quantification of confocal imagesignals and to O. Dominguez for troubleshooting with cloning and sequencing. We thank S. Llanos for the p21 promoter reporter (described in ref. 33). Research in the Blasco lab is funded by the Spanish Ministry of Economy and Competitiveness Project (SAF2013-45111-R), the Madrid Regional Government Project S2010/BMD-2303 (ReCaRe),Fundacio´n Botı´n (Spain) and AXA Research Fund (AXA 2011, Spain).S

Astrocyte Activation via Stat3 Signaling Determines the Balance of Oligodendrocyte versus Schwann Cell Remyelination.

Remyelination within the central nervous system (CNS) most often is the result of oligodendrocyte progenitor cells differentiating into myelin-forming oligodendrocytes. In some cases, however, Schwann cells, the peripheral nervous system myelinating glia, are found remyelinating demyelinated regions of the CNS. The reason for this peripheral type of remyelination in the CNS and what governs it is unknown. Here, we used a conditional astrocytic phosphorylated signal transducer and activator of transcription 3 knockout mouse model to investigate the effect of abrogating astrocyte activation on remyelination after lysolecithin-induced demyelination of spinal cord white matter. We show that oligodendrocyte-mediated remyelination decreases and Schwann cell remyelination increases in lesioned knockout mice in comparison with lesioned controls. Our study shows that astrocyte activation plays a crucial role in the balance between Schwann cell and oligodendrocyte remyelination in the CNS, and provides further insight into remyelination of CNS axons by Schwann cells.The work was funded by grants from the UK Multiple Sclerosis Society. GMdC received financial support from CNPq 200993/2010-0; Ciência Sem Fronteiras CNPq 201797/2011-9.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.ajpath.2015.05.01

Chiral Antioxidant-based Gold Nanoclusters Reprogram DNA Epigenetic Patterns

Epigenetic modifications sit ‘on top of’ the genome and influence DNA transcription, which can force a significant impact on cellular behavior and phenotype and, consequently human development and disease. Conventional methods for evaluating epigenetic modifications have inherent limitations and, hence, new methods based on nanoscale devices are needed. Here, we found that antioxidant (glutathione) chiral gold nanoclusters induce a decrease of 5-hydroxymethylcytosine (5hmC), which is an important epigenetic marker that associates with gene transcription regulation. This epigenetic change was triggered partially through ROS activation and oxidation generated by the treatment with glutathione chiral gold nanoclusters, which may inhibit the activity of TET proteins catalyzing the conversion of 5-methylcytosine (5mC) to 5hmC. In addition, these chiral gold nanoclusters can downregulate TET1 and TET2 mRNA expression. Alteration of TET-5hmC signaling will then affect several downstream targets and be involved in many aspects of cell behavior. We demonstrate for the first time that antioxidant-based chiral gold nanomaterials have a direct effect on epigenetic process of TET-5hmC pathways and reveal critical DNA demethylation patterns

Toma de decisiones a través del trabajo colaborativo en adolescentes [Decision-making through collaborative work in adolescents]

El presente trabajo describe los avances del primer acercamiento de un proyecto, realizado en una telesecundaria ubicada en Palma Sola, siendo esta una comunidad de Coatzintla, Ver. México, donde participan 27 alumnos: 14 de 2º A y 13 de 2º B. Se describen dos etapas esenciales para el proyecto como lo es el primer acercamiento y el diagnostico formal la cual ayuda a delimitar la problemática en la que se actuará. Sustentado en el desarrollo de la toma de decisiones y resolución de conflictos basados en las habilidades para la vida, propuesta por la OMS en 1993, bajo la metodología de investigación-acción en donde las primeras etapas son el primer acercamiento y detección de necesidades lo cual nos lleva a resultados de un primer diagnóstico. Se propone el aprendizaje colaborativo como estrategia para el desarrollo de la toma de decisiones en los estudiantes. Es aquí, donde se identifica que los estudiantes de 2º A y 2º B presentan bajo rendimiento en todas las asignaturas siendo los más bajos en el historial administrativo de la telesecundaria “Adolfo López Mateos”, también muestran conflictos socioemocionales y áreas de oportunidad en la toma de decisiones y resolución de conflictos. Lo que se busca como objetivo primordial en el presente escrito es identificar las necesidades individuales y grupales de los adolescentes por medio de un diagnostico formal que a futuro permita el diseño de un plan de acción para el desarrollo de la toma de decisiones. [This paper describes the advances of the first approach of a project, realized in a telesecundaria (Mexican TV learning system) located in Palma Sola, being a community of Coatzintla, Ver. Mexico, where 27 students participate: 14 of 2º A and 13 of 2º B. Two essential stages for the project are described as the first approach and the formal diagnosis which helps to delimit the problematic in which to act. Sustained in the development of decision-making and conflict resolution based on life skills, proposed by OMS in 1993, under the methodology of action research where the first stages are the first approach and detection of needs which Leads us to the results of a first diagnosis. Collaborative learning is proposed as a strategy for the development of decision making in students. It is here, where it is identified that the students of 2º A and 2º B present low performance in all the subjects being the lowest in the administrative history of the telesecondary "Adolfo López Mateos", also show socioemotional conflicts and areas of opportunity in the taking Decision-making and conflict resolution. What is sought as a primary objective in this paper is to identify the individual and group needs of the participants through a formal diagnosis that in the future allows the design of an action plan for the development of decision making.

Effects of different arachidonic acid supplementation on psychomotor development in very preterm infants; A randomized controlled trial

Background & aims: Nutritional supplementation with polyunsaturated fatty acids is important in preterm infants neurodevelopment, but it is not known if the omega-6/omega-3 ratio affects this process. This study was designed to determine the effects of a balanced contribution of arachidonic acid in very preterm newborns fed with formula milk. Methods: This was a randomized trial, in which newborns <1500 g and/or <32 weeks gestational age were assigned to one of two groups, based on the milk formula they would receive during the first year of life. Initially, 60 newborns entered the study, but ultimately, group A was composed of 24 newborns, who were given formula milk with an ω-6/ ω-3 ratio of 2/1, and Group B was composed of 21 newborns, given formula milk with an ω-6/ω-3 ratio of 1/1. The infants were followed up for two years: growth, visual-evoked potentials, brainstem auditory-evoked potentials, and plasma fatty acids were periodically measured, and psychomotor development was assessed using the Brunet Lézine scale at 24 months corrected age. A control group, for comparison of Brunet Lézine score, was made up of 25 newborns from the SEN1500 project, who were fed exclusively with breast milk. Results: At 12 months, arachidonic acid values were significantly higher in group A than in group B (6.95 ± 1.55 % vs. 4.55 ± 0.78 %), as were polyunsaturated fatty acids (41.02 ± 2.09 % vs. 38.08 ± 2.32 %) achieved a higher average. Group A achieved a higher average Brunet Lézine score at 24 months than group B (99.9 ± 9 vs. 90.8 ± 11, p =0.028). The Brunet Lézine results from group A were compared with the control group results, with very similar scores registered between the two groups (99.9 ± 9 vs. 100.5 ± 7). There were no significant differences in growth or evoked potentials between the two formula groups. Conclusions: Very preterm infants who received formula with an ω-6/ω-3 ratio of 2/1 had higher blood levels of essential fatty acids during the first year of life, and better psychomotor development, compared with very preterm newborns who consumed formula with an ω-6/ω-3 of 1/1. Therefore, formula milk with an arachidonic acid quantity double that of docosahexaenoic acid should be considered for feeding very preterm infants

Intersections of quadrics, moment-angle manifolds, and Hamiltonian-minimal Lagrangian embeddings

We study the topology of Hamiltonian-minimal Lagrangian submanifolds N in C^m constructed from intersections of real quadrics in a work of the first author. This construction is linked via an embedding criterion to the well-known Delzant construction of Hamiltonian toric manifolds. We establish the following topological properties of N: every N embeds as a submanifold in the corresponding moment-angle manifold Z, and every N is the total space of two different fibrations, one over the torus T^{m-n} with fibre a real moment-angle manifold R, and another over a quotient of R by a finite group with fibre a torus. These properties are used to produce new examples of Hamiltonian-minimal Lagrangian submanifolds with quite complicated topology.Comment: 14 pages, published version (minor changes

Flavonoid content of selected foods – A comparison of four international composition tables

The content of flavonoids, widely found in plant-based foods, might differ depending on which food composition table (FCT) is being used. In this study, we investigated the variation and comparability in the flavonoid content of selected foods across four international food composition tables. Flavonoid estimates were derived for all foods available in each table, and comparisons were carried out for foods common between tables. Bias percentage, 95 % limits of agreement, and intra-class correlation coefficients (ICCs; 95 % confidence intervals [95 %CI]) were estimated. Phenol-Explorer and Indian FCT showed moderate level of agreement for total flavonoid (ICC 0.50 and 0.57 respectively) when compared to the USDA table. eBASIS for total flavonoids and anthocyanidins (ICC 0.67 and 0.85, respectively), and Indian FCT for flavanols and flavanones (ICC 0.71 and ICC 0.85, respectively) showed moderate-to-good level of agreement, and low level of agreement for other subclasses when compared to Phenol Explorer. Several flavonoid subclasses showed low to moderate levels of agreement between FCTs, whilst others (including total flavonoid intake) had lower levels of agreement. Methodological approaches in the measurement of flavonoid content of foods across tables, and continued efforts to improve harmonization of these databases would contribute to improve quantification of flavonoid content. © 2024 The Authors"We are grateful to the National Institute of Nutrition in Hyderabad and to the e-BASIS Consortium for supporting this research and for facilitating access to their food composition tables and for answering queries related to their content. M.A.A. gratefully acknowledges the ‘Emerging Leaders in Nutrition Science Award’ by the American Society of Nutrition (ASN) for the presentation of an abstract with preliminary results from this manuscript; and The Barbara and Richard Hall Student Award for Excellence in Nutrition Science, conferred by the Center for Human Nutrition at the Johns Hopkins Bloomberg School of Public Health. MAA received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 754345-INVITE. The UK’s Medical Research Council (MR/R011192/1) funds the BOLD Study.

Regulation of cell protrusions by small GTPases during fusion of the neural folds.

Epithelial fusion is a crucial process in embryonic development, and its failure underlies several clinically important birth defects. For example, failure of neural fold fusion during neurulation leads to open neural tube defects including spina bifida. Using mouse embryos, we show that cell protrusions emanating from the apposed neural fold tips, at the interface between the neuroepithelium and the surface ectoderm, are required for completion of neural tube closure. By genetically ablating the cytoskeletal regulators Rac1 or Cdc42 in the dorsal neuroepithelium, or in the surface ectoderm, we show that these protrusions originate from surface ectodermal cells and that Rac1 is necessary for the formation of membrane ruffles which typify late closure stages, whereas Cdc42 is required for the predominance of filopodia in early neurulation. This study provides evidence for the essential role and molecular regulation of membrane protrusions prior to fusion of a key organ primordium in mammalian development