Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome Sequencing in Open Microfabricated High Density Picoliter Reactors

We describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel 60×60 mm2 fibreoptic slide containing 1,600,000 individual wells and is able to sequence 25 million bases, at 99% or better accuracy (phred 20), in a 4 hour run. To provide sequencing templates, we clonally amplify DNA fragments on beads in the droplets of an emulsion. The template-carrying beads are loaded into the wells to convert each into a picoliter-scale sequencing reactor. We perform sequencing by synthesis using a pyrosequencing protocol optimized for solid support and the small dimension of the open reactors. Here we show the utility, throughput, accuracy and robustness of this system by shotgun sequencing and de novo assembling the Mycoplasma genitalium genome with 96% coverage at 99.96 % accuracy in one run of the machine. DNA sequencing has dramatically changed the nature of biomedical research and medicine. Reductions in the cost, complexity and time required to sequence large amount of DNA, including improvements in the ability to sequence bacterial and eukaryotic genomes will have significant scientific, economic and cultural impact. Large scale sequencing projects, including whole genome sequencing, have usually required the cloning of DNA fragments into bacterial vectors, amplification and purification of individual templates, followed by Sanger sequencing 1 using fluorescent chain-terminating nucleotide analogues 2 and either slab gel or capillary electrophoresis. Current estimates put the cost of sequencing a human genome between $10 Correspondence and requests for materials should be addressed to J. M. Rothberg (jrothberg@454.com). Sequences for M. genitalium and S. pneumoniae were deposited at DDBJ/EMBL/GenBank under accession numbers AAGX01000000 and AAGY01000000 respectively. *These authors contributed equally to the work. Supplementary Information accompanies the paper on www.nature. com/nature. NIH Public Access
Shared and distinct retinal input to the mouse superior colliculus and dorsal lateral geniculate nucleus

Our results suggest that the mouse superior colliculus (SC) has access to input from most of the retinal ganglion cells (RGCs) that innervate the dorsal lateral geniculate nucleus (dLGN). By comparison, a number of RGC types appear to innervate the SC but not the dLGN; these RGCs generally exhibit more transient responses and respond best to small stimuli.
Trends in excess of weight, underweight and adiposity among Spanish children from 2004 to 2010: the Cuenca Study

Abstract Objective To examine the trends in BMI and adiposity among schoolchildren from Cuenca, Spain, during 2004–2010. Design Two methodologically comparable surveys were carried out in 2004 and 2010. Setting Primary schools in Cuenca, a province in the middle of Spain. Subjects All schoolchildren aged 8–11 years, belonging to 4th and 5th grades from twenty schools in the Province of Cuenca, were invited to participate in both cross-sectional studies. Weight, height and body fat percentage (BF%) from bioelectrical impedance were measured with standardized procedures. Results The study included 550 boys and 539 girls in 2004, and 569 boys and 531 girls in 2010. In 2010, 8·1 % of children were underweight, 25·9 % overweight and 9·5 % obese. From 2004 to 2010, the prevalence of overweight rose from 21·6 % to 28·0 % (P = 0·004) and BF % increased from 22·6 % to 24·0 % (P = 0·001) among boys. No change was observed in overweight and BF % in girls, or in underweight and obesity in either sex. In boys, most of the distribution of BMI and BF % shifted to the right; in contrast, among girls no substantial change was apparent in the distribution of BMI and BF %. Conclusions From 2004 to 2010 the prevalence of overweight and adiposity has continued to increase among boys. However, the obesity epidemic may have levelled off in girls. Given that the prevalence of childhood excess weight is still very high, the current evidence-based efforts to halt the obesity epidemic in Spain should be strengthened.
Disruption of an N-acetyltransferase gene in the silkworm reveals a novel role in pigmentation

The pigmentation of insects has served as an excellent model for the study of morphological trait evolution and developmental biology. The melanism (mln) mutant of the silkworm Bombyx mori is notable for its strong black coloration, phenotypic differences between larval and adult stages, and its widespread use in strain selection. Here, we report the genetic and molecular bases for the formation of the mln morphological trait. Fine mapping revealed that an arylalkylamine N-acetyltransferase (AANAT) gene co-segregates with the black coloration patterns. Coding sequence variations and expression profiles of AANAT are also associated with the melanic phenotypes. A 126 bp deletion in the mln genome causes two alternatively spliced transcripts with premature terminations. An enzymatic assay demonstrated the absolute loss of AANAT activity in the mutant proteins. We also performed RNA interference of AANAT in wild-type pupae and observed a significant proportion of adults with ectopic black coloration. These findings indicate that functional deletion of this AANAT gene accounts for the mln mutation in silkworm. AANAT is also involved in a parallel melanin synthesis pathway in which ebony plays a role, whereas no pigmentation defect has been reported in the Drosophila model or in other insects to date. To the best of our knowledge, the mln mutation is the first characterized mutant phenotype of insects with AANAT, and this result contributes to our understanding of dopamine metabolism and melanin pattern polymorphisms.
The Paleoanthropocene of the Yucatán Peninsula: palynological evidence of environmental change

espanolLas actividades humanas han influenciado sobre los paisajes de la peninsula de Yucatan desde mas de 4000 anos. Varios estudios paleoecologicos muestran actividades de agricultura, el registro polinico mas antiguo de maiz (Zea mays L.) proviene del norte de Belice, con una edad aproximada de 3300 BC. Otros estudios paleoecologicos del norte de Guatemala y de la porcion mexicana de la peninsula de Yucatan muestran registros de maiz fosil con rangos de edad desde 1500 a 3000 A.C. La mayoria de los registros muestran una marcada tendencia a condiciones de mayor sequia despues de los 3500 A.C. Estas tendencias de sequia se registran como reduccion del polen fosil arboreo. El registro polinico de Z. mays esta acompanado de taxa que indican diferentes grados de perturbacion en la vegetacion natural. EnglishHuman activities have changed and shaped landscape conditions of the Yucatan Peninsula for more than 4000 years. Several paleoecological studies showed the oldest pollen record of corn-based agriculture is from northern Belize, with an estimated age of 3300 BC. Several other studies report maize between 1500 and 3000 BC from northern Guatemala and the Mexican part of the Yucatan Peninsula. After 3500 cal yr BP several paleoecological studies showed a marked tendency to drier climatic conditions. In pollen records, increased drought is expressed as a reduced presence of fossil arboreal pollen. Pollen records with the presence of Zea mays also show other taxa, which are indicators of disturbance in different vegetation types.
Polymerization of Purified Yeast Septins: Evidence That Organized Filament Arrays May Not Be Required for Septin Function

The septins are a family of proteins required for cytokinesis in a number of eukaryotic cell types. In budding yeast, these proteins are thought to be the structural components of a filament system present at the mother–bud neck, called the neck filaments. In this study, we report the isolation of a protein complex containing the yeast septins Cdc3p, Cdc10p, Cdc11p, and Cdc12p that is capable of forming long filaments in vitro. To investigate the relationship between these filaments and the neck filaments, we purified septin complexes from cells deleted for CDC10 or CDC11. These complexes were not capable of the polymerization exhibited by wild-type preparations, and analysis of the neck region by electron microscopy revealed that the cdc10Δ and cdc11Δ cells did not contain detectable neck filaments. These results strengthen the hypothesis that the septins are the major structural components of the neck filaments. Surprisingly, we found that septin dependent processes like cytokinesis and the localization of Bud4p to the neck still occurred in cdc10Δ cells. This suggests that the septins may be able to function in the absence of normal polymerization and the formation of a higher order filament structure.
Activity recognition in smart homes based on electrical devices identification

Activity recognition constitutes the key challenge in the development of smart home assistive systems. In this paper, we propose a new algorithmic method for activity recognition in a smart home, based on load signatures of appliances. Most recognition approaches rely on distributed and heterogeneous sensors (ex. RFID), which are intrusive require complex installation, deployment and maintenance. On the other hand, most applications of appliance load monitoring (signal analysis) refer to the energy saving and the costs reducing of energy consumption. Consequently, our proposal constitutes an original application and new algorithmic method based on steady-state operations and signatures. The extraction process of load signatures of appliances is carried out in a three-dimensional space through a single power analyzer, which is non-intrusive (NIALM). We have rigorously tested this new approach by conducting an experiment in our smart home prototype by simulating daily scenarios taken from clinical trials previously done with Alzheimer patients. The promising results we obtained are presented and compared to other approaches, showing that, with an exceptionally minimal investment and the exploitation of relatively limited data, our method can efficiently recognize activities of daily living for providing assistive services.
Evolving cognitive and social experience in Particle Swarm Optimization through Differential Evolution

In recent years, the Particle Swarm Optimization has rapidly gained increasing popularity and many variants and hybrid approaches have been proposed to improve it. Motivated by the behavior and the proximity characteristics of the social and cognitive experience of each particle in the swarm, we develop a hybrid approach that combines the Particle Swarm Optimization and the Differential Evolution algorithm. Particle Swarm Optimization has the tendency to distribute the best personal positions of the swarm near to the vicinity of problem's optima. In an attempt to efficiently guide the evolution and enhance the convergence, we evolve the personal experience of the swarm with the Differential Evolution algorithm. Extensive experimental results on twelve high dimensional multimodal benchmark functions indicate that the hybrid variants are very promising and improve the original algorithm.
Exploring the Use of Concern Element Role Information in Feature Location Evaluation

Before making changes, programmers need to locate and understand source code that corresponds to specific functionality, i.e., Perform concern or feature location. Numerous concern and feature location techniques have been proposed, but to the best of our knowledge, no existing techniques or evaluations report information on what role a code element plays in the larger concern. In this paper, we report on two case studies that investigate two hypotheses on how evaluation studies of concern location techniques can be strengthened by utilizing concern role information: (1) by increasing agreement among human annotators for gold set establishment and (2) by providing richer information about the elements ranked as relevant by concern location techniques, which could help further improve the tools. We conducted a case study of 6 Java developers annotating 3 concerns with role information. When the developers understood the task description, pair wise agreement increased by 20%, 25%, and 135% for the 3 concerns over a prior concern location study without role information. Our findings also suggest that there may be core element roles that need to be annotated by humans, but that the remaining roles may be automatically derived, which could facilitate more reliable concern location benchmarks in the future. We also conducted an exploratory study of the element roles represented in results returned by a state of the art feature location tool. The results of these two studies suggest that integrating concern element role information into evaluations can help to strengthen both the gold set establishment and the analysis of results returned by various tools.
Chronically Epileptic Human and Rat Neocortex Display a Similar Resistance Against Spreading Depolarization In Vitro

Background and Purpose— Experimental and clinical evidence suggests that prolonged spreading depolarizations (SDs) are a promising target for therapeutic intervention in stroke because they recruit tissue at risk into necrosis by protracted intracellular calcium surge and massive glutamate release. Unfortunately, unlike SDs in healthy tissue, they are resistant to drugs such as N-methyl-d-aspartate-receptor antagonists. This drug resistance of SD in low perfusion areas may be due to the gradual rise of extracellular potassium before SD onset. Brain slices from patients undergoing surgery for intractable epilepsy allow for screening of drugs, targeting pharmacoresistant SDs under elevated potassium in human tissue. However, network changes associated with epilepsy may interfere with tissue susceptibility to SD. This could distort the results of pharmacological tests. Methods— We investigated the threshold for SD, induced by a gradual rise of potassium, in neocortex slices of patients with intractable epilepsy and of chronically epileptic rats as well as age-matched and younger control rats using combined extracellular potassium/field recordings and intrinsic optical imaging. Results— Both age and epilepsy significantly increased the potassium threshold, which was similarly high in epileptic rat and human slices (23.6±2.4 mmol/L versus 22.3±2.8 mmol/L). Conclusions— Our results suggest that chronic epilepsy confers resistance against SD. This should be considered when human tissue is used for screening of neuroprotective drugs. The finding of similar potassium thresholds for SD in epileptic human and rat neocortex challenges previous speculations that the resistance of the human brain against SD is markedly higher than that of the rodent brain.
Comparative analysis of meteorological and hydrological drought over the Pearl River basin in southern China

Drought is one of the major natural hazards with a possibly devastating impact on the regional environment, agriculture, and water resources. Previous studies have assessed the historic changes in meteorological drought over various regional scales but have rarely considered hydrological drought due to limited hydrological observations. Here, we use long-term (1960–2012) hydro-meteorological data to analyze the meteorological and hydrological drought comparatively in the Pearl River basin (PRB) in southern China using the standardized precipitation index (SPI) and the standardized runoff index (SRI). The results indicate a strong positive correlation between the SPI and SRI, and the correlation tends to be stronger at the longer timescale. The SPI is reliable to substitute for the SRI to represent the hydrological drought at the long-term scale (e.g., 12 months or longer). Trend analysis reveals a noticeably wetting trend mainly in the eastern regions and a significant drying trend mainly in the western regions and the downstream area of the PRB. The drought frequency is spatially heterogeneous and varies slightly at the interannual scale. Overall, the drought is dominated by noticeable cycles of shorter periodicity (0.75–1.8 years), and periodic cycles in the meteorological drought are mainly responsible for those in the hydrological drought.
Immunologic and biochemical characterization of homozygous and heterozygous Glanzmann thrombasthenia in the Iraqi‐Jewish and Arab populations of Israel: comparison of techniques for carrier detection

Summary To define biochemically and immunologically the platelet defect in Iraqi‐Jews and Arabs with Glanzmann thrombasthenia in Israel, we tested the platelets of 32 thrombasthenics and 37 obligate carriers from 19 families with affected members. Thrombasthenic platelets were devoid of glycoprotein IIb (GPIIb) as judged by polyacrylamide gel electrophoresis and devoid of the GPIIb/IIIa complex as judged by radio‐electroimmunoassay. Binding of a murine monoclonal antibody directed at GPIIb and/or GPIIIa to intact thrombasthenic platelets averaged less than 2% of the control value. Evaluation of the number of molecules of antibody bound per platelet permitted discrimination between controls and obligate carriers with a high degree of accuracy (sensitivity = 91.9%, specificity = 92.3%). Obligate carriers could also be discriminated from controls by determining the ratio of GPIIb to GPIb by polyacrylamide gel electrophoresis and by quantifying the GPIIb/IIIa complex by radio‐electroimmunoassay. These studies indicate that the thrombasthenics in Israel have the severe form of the disease (type I) and that the platelets of heterozygotes have significantly reduced amounts of both total and surface‐exposed GPIIb and/or GPIIIa.
Proteomics of Skeletal Muscle: Focus on Insulin Resistance and Exercise Biology

Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is caused by a decreased ability of muscle to respond to circulating insulin. Physical exercise improves insulin sensitivity and whole body metabolism and remains one of the most promising interventions for the prevention of Type 2 diabetes. Insulin resistance and exercise adaptations in skeletal muscle might be a cause, or consequence, of altered protein expressions profiles and/or their posttranslational modifications (PTMs). Mass spectrometry (MS)-based proteomics offer enormous promise for investigating the molecular mechanisms underlying skeletal muscle insulin resistance and exercise-induced adaptation; however, skeletal muscle proteomics are challenging. This review describes the technical limitations of skeletal muscle proteomics as well as emerging developments in proteomics workflow with respect to samples preparation, liquid chromatography (LC), MS and computational analysis. These technologies have not yet been fully exploited in the field of skeletal muscle proteomics. Future studies that involve state-of-the-art proteomics technology will broaden our understanding of exercise-induced adaptations as well as molecular pathogenesis of insulin resistance. This could lead to the identification of new therapeutic targets.
Electroporated Antigen-Encoding mRNA Is Not a Danger Signal to Human Mature Monocyte-Derived Dendritic Cells

For therapeutic cancer vaccination, the adoptive transfer of mRNA-electroporated dendritic cells (DCs) is frequently performed, usually with monocyte-derived, cytokine-matured DCs (moDCs). However, DCs are rich in danger-sensing receptors which could recognize the exogenously delivered mRNA and induce DC activation, hence influencing the DCs' immunogenicity. Therefore, we examined whether electroporation of mRNA with a proper cap and a poly-A tail of at least 64 adenosines had any influence on cocktail-matured moDCs. We used 16 different RNAs, encoding tumor antigens (MelanA, NRAS, BRAF, GNAQ, GNA11, and WT1), and variants thereof. None of those RNAs induced changes in the expression of CD25, CD40, CD83, CD86, and CD70 or the secretion of the cytokines IL-8, IL-6, and TNFα of more than 1.5-fold compared to the control condition, while an mRNA encoding an NF-κB-activation protein as positive control induced massive secretion of the cytokines. To determine whether mRNA electroporation had any effect on the whole transcriptome of the DCs, we performed microarray analyses of DCs of 6 different donors. None of 60,000 probes was significantly different between mock-electroporated DCs and MelanA-transfected DCs. Hence, we conclude that no transcriptional programs were induced within cocktail-matured DCs by electroporation of single tumor-antigen-encoding mRNAs.
Approximating Semi-matchings in Streaming and in Two-Party Communication

We study the streaming complexity and communication complexity of approximating unweighted semi-matchings. A semi-matching in a bipartite graph G = (A, B, E) with n = |A| is a subset of edges S⊆E that matches all A vertices to B vertices with the goal usually being to do this as fairly as possible. While the term semi-matching was coined in 2003 by Harvey et al. [2003], the problem had already previously been studied in the scheduling literature under different names. We present a deterministic one-pass streaming algorithm that for any 0 ⩽ ε ⩽ 1 uses space Õ(n1+ε and computes an O(n(1−ε)/2)-approximation to the semi-matching problem. Furthermore, with O(log n) passes it is possible to compute an O(log n)-approximation with space Õ(n). In the one-way two-party communication setting, we show that for every ε > 0, deterministic communication protocols for computing an O(n1/(1+ε)c+1)-approximation require a message of size more than cn bits. We present two deterministic protocols communicating n and 2n edges that compute an O√n and an O(n1/3)-approximation, respectively. Finally, we improve on the results of Harvey et al. [2003] and prove new links between semi-matchings and matchings. While it was known that an optimal semi-matching contains a maximum matching, we show that there is a hierarchical decomposition of an optimal semi-matching into maximum matchings. A similar result holds for semi-matchings that do not admit length-two degree-minimizing paths.