Miracle-dz/UniFAR-FTUs huggingface dataset:
Mining proteomic data to expose protein modifications in Methanosarcina mazei strain Gö1

Proteomic tools identify constituents of complex mixtures, often delivering long lists of identified proteins. The high-throughput methods excel at matching tandem mass spectrometry data to spectra predicted from sequence databases. Unassigned mass spectra are ignored, but could, in principle, provide valuable information on unanticipated modifications and improve protein annotations while consuming limited quantities of material. Strategies to “mine” information from these discards are presented, along with discussion of features that, when present, provide strong support for modifications. In this study we mined LC-MS/MS datasets of proteolytically-digested concanavalin A pull down fractions from Methanosarcina mazei Gö1 cell lysates. Analyses identified 154 proteins. Many of the observed proteins displayed post-translationally modified forms, including O-formylated and methyl-esterified segments that appear biologically relevant (i.e., not artifacts of sample handling). Interesting cleavages and modifications (e.g., S-cyanylation and trimethylation) were observed near catalytic sites of methanogenesis enzymes. Of 31 Methanosarcina protein N-termini recovered by concanavalin A binding or from a previous study, only M. mazei S-layer protein MM1976 and its M. acetivorans C2A orthologue, MA0829, underwent signal peptide excision. Experimental results contrast with predictions from algorithms SignalP 3.0 and Exprot, which were found to over-predict the presence of signal peptides. Proteins MM0002, MM0716, MM1364, and MM1976 were found to be glycosylated, and employing chromatography tailored specifically for glycopeptides will likely reveal more. This study supplements limited, existing experimental datasets of mature archaeal N-termini, including presence or absence of signal peptides, translation initiation sites, and other processing. Methanosarcina surface and membrane proteins are richly modified.
Polarimetric SAR images classification based on L distribution and spatial context

To obtain accurate classification results of polarimetric SAR images in different heterogeneity areas, a novel unsupervised classification method is proposed, which combines an advanced distribution with spatial contextual information based on stochastic expectation maximization (SEM) algorithm. Specifically, the probabilities of class membership are calculated by L distribution, and a neighborhood function is defined to describe spatial contextual information. Then the probabilities of class membership are altered by the predefined neighborhood function via probabilistic label relaxation (PLR) technique. Moreover, RADARSAT-2 and EMISAR data are used to verify the effectiveness of the proposed method. The experiment results show it can accurately classify different heterogeneity areas and obtain more consistent results compared with other algorithms.
Universes in type theory part I—Inaccessibles and Mahlo

We give an overview over universes in Martin-Lof type theory and consider the following universe constructions: a simple universe, E. Palmgren’s super universe and the Mahlo universe. We then introduce models for these theories in extensions of Kripke-Platek set theory having the same proof theoretic strength. The extensions of Kripke-Platek set theory used formalise the existence of a recursively inaccessible ordinal, a recursively hyper-inaccessible ordinal, and a recursively Mahlo ordinal. Using these models we determine upper bounds for the proof theoretic strength of the theories in questions. In case of simple universes and the Mahlo universe, these bounds have been shown by the author to be sharp. This article is an overview over the main techniques in developing these models, full details will be presented in a series of future articles.
Design and evaluation of menu systems for immersive virtual environments

Interfaces for system control tasks in virtual environments (VEs) have not been extensively studied. The paper focuses on various types of menu systems to be used in such environments. We describe the design of the TULIP menu, a menu system using Pinch Gloves/sup TM/, and compare it to two common alternatives: floating menus and pen and tablet menus. These three menus were compared in an empirical evaluation. The pen and tablet menu was found to be significantly faster, while users had a preference for TULIP. Subjective discomfort levels were also higher with the floating menus and pen and tablet.
The development of peripheral fatigue and short‐term recovery during self‐paced high‐intensity exercise

In this study we describe the time course of fatigue development during and after an intense bout of self‐paced, high‐intensity dynamic exercise using various electrical stimulation parameters to assess neuromuscular function (NMF) changes. Most of the decrease in muscle function occurs within the first 40% of the exercise bout, and substantial recovery in muscle function occurs within 1–2 min after exercise termination. Decreases in muscle function varied greatly with different methods of stimulation, suggesting that the extent to which muscle fatigue is documented during exercise depends upon NMF assessment methodology. Measurements of muscle function must be performed as soon as possible after exercise termination, and previous studies may have underestimated the extent to which muscle fatigue develops during exercise.
Conflict, Decentralisation and Local Governance in Colombia, 1974-2004

The objective of this paper is to determine the variables that explain the geographical expansion and armed activity of Colombian irregular groups since the mid seventies, taking into account the role of the political, fiscal and budgetary decentralization and its effects over local governance. This period of Colombian history (1974-2004) has been graved by strong economic, social and institutional changes that have deepened particularly since the decentralization process of the mid eighties. In fact, this paper states that decentralization process transformed the conflict into a dispute over the local power, intensifying the use of violence in order to appropriate part of the public goods and resources, interfere the political process and consolidate the group´s territorial control. The analysis of the illegal group´s early activity (1974-1982) shows that the use of violence is explained by grievances such as poverty or inequality. However, subsequent years reveal deep changes in the illegal group´s strategic procedures in which the decentralization process have given them incentives to control the local governments by using violence (greed). The results demonstrate a strong and significant relationship between the intensification of the armed conflict and the greater political, budgetary and fiscal autonomy of local governments. In fact, the presence of local resources such as royalties and taxes triggers violence against politicians being more intense in the municipalities where the actions of the illegal groups are higher.
Design and Validation of a Rehabilitation Robotic Exoskeleton for Tremor Assessment and Suppression

Exoskeletons are mechatronic systems worn by a person in such a way that the physical interface permits a direct transfer of mechanical power and exchange of information. Upper limb robotic exoskeletons may be helpful for people with disabilities and/or limb weakness or injury. Tremor is the most common movement disorder in neurological practice. In addition to medication, rehabilitation programs, and deep brain stimulation, biomechanical loading has appeared as a potential tremor suppression alternative. This paper introduces the robotic exoskeleton called WOTAS (wearable orthosis for tremor assessment and suppression) that provides a means of testing and validating nongrounded control strategies for orthotic tremor suppression. This paper describes in detail the general concept for WOTAS, outlining the special features of the design and selection of system components. Two control strategies developed for tremor suppression with exoskeletons are described. These two strategies are based on biomechanical loading and notch Altering the tremor through the application of internal forces. Results from experiments using these two strategies on patients with tremor are summarized. Finally, results from clinical trials are presented, which indicate the feasibility of ambulatory mechanical
Construction of a reference gene association network from multiple profiling data: application to data analysis

MOTIVATION Gene expression profiling is an important tool for gaining insight into biology. Novel strategies are required to analyze the growing archives of microarray data and extract useful information from them. One area of interest is in the construction of gene association networks from collections of profiling data. Various approaches have been proposed to construct gene networks using profiling data, and these networks have been used in functional inference as well as in data visualization. Here, we investigated a non-parametric approach to translate profiling data into a gene network. We explored the characteristics and utility of the resulting network and investigated the use of network information in analysis of variance models and hypothesis testing. RESULTS Our work is composed of two parts: gene network construction and partitioning and hypothesis testing using sub-networks as groups. In the first part, multiple independently collected microarray datasets from the Gene Expression Omnibus data repository were analyzed to identify probe pairs that are positively co-regulated across the samples. A co-expression network was constructed based on a reciprocal ranking criteria and a false discovery rate analysis. We named this network Reference Gene Association (RGA) network. Then, the network was partitioned into densely connected sub-networks of probes using a multilevel graph partitioning algorithm. In the second part, we proposed a new, MANOVA-based approach that can take individual probe expression values as input and perform hypothesis testing at the sub-network level. We applied this MANOVA methodology to two published studies and our analysis indicated that the methodology is both effective and sensitive for identifying transcriptional sub-networks or pathways that are perturbed across treatments.
Modelling primaquine-induced haemolysis in G6PD deficiency

Primaquine is the only drug available to prevent relapse in vivax malaria. The main adverse effect of primaquine is erythrocyte age and dose-dependent acute haemolytic anaemia in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd). As testing for G6PDd is often unavailable, this limits the use of primaquine for radical cure. A compartmental model of the dynamics of red blood cell production and destruction was designed to characterise primaquine-induced haemolysis using a holistic Bayesian analysis of all published data and was used to predict a safer alternative to the currently recommended once weekly 0.75 mg/kg regimen for G6PDd. The model suggests that a step-wise increase in daily administered primaquine dose would be relatively safe in G6PDd. If this is confirmed, then were this regimen to be recommended for radical cure patients would not require testing for G6PDd in areas where G6PDd Viangchan or milder variants are prevalent. DOI: http://dx.doi. org/10.7554/eLife.23061. 001
Dirofilaria immitis in Red Foxes (Vulpes vulpes) in an Endemic Area Near Sydney, Australia

Received for publication 19 May 1983. americana) (Thorne, 1982, Diseases of Wildlife in Wyoming, 2nd ed., Wyo. Game and Fish Dept., Cheyenne, Wyoming, 353 pp.). These abscesses were found most commonly between large muscles of the legs. The condition is not readily transmissible from one individual to another. This is the first report of C. pyogenes from B. bison. The hepatomegaly and adhesions observed in the present case are believed to be a result of the infection. It appears as if the current case was an isolated incident with few serious implications for the health and welfare of the Delta Junction bison herd. Financial support for this investigation was provided by Federal Aid in Wildlife Restoration Project W-22-2.
Response regulator output in bacterial chemotaxis

Chemotaxis responses in Escherichia coli are mediated by the phosphorylated response‐regulator protein P‐CheY. Biochemical and genetic studies have established the mechanisms by which the various components of the chemotaxis system, the membrane receptors and Che proteins function to modulate levels of CheY phosphorylation. Detailed models have been formulated to explain chemotaxis sensing in quantitative terms; however, the models cannot be adequately tested without knowledge of the quantitative relationship between P‐CheY and bacterial swimming behavior. A computerized image analysis system was developed to collect extensive statistics on freeswimming and individual tethered cells. P‐CheY levels were systematically varied by controlled expression of CheY in an E.coli strain lacking the CheY phosphatase, CheZ, and the receptor demethylating enzyme CheB. Tumbling frequency was found to vary with P‐CheY concentration in a weakly sigmoidal fashion (apparent Hill coefficient ∼2.5). This indicates that the high sensitivity of the chemotaxis system is not derived from highly cooperative interactions between P‐CheY and the flagellar motor, but rather depends on nonlinear effects within the chemotaxis signal transduction network. The complex relationship between single flagella rotation and free‐swimming behavior was examined; our results indicate that there is an additional level of information processing associated with interactions between the individual flagella. An allosteric model of the motor switching process is proposed which gives a good fit to the observed switching induced by P‐CheY. Thus the level of intracellular P‐CheY can be estimated from behavior determinations: ∼30% of the intracellular pool of CheY appears to be phosphorylated in fully adapted wild‐type cells.
Dissipative soliton resonance as a guideline for high-energy pulse laser oscillators

J. M. Soto-Crespo acknowledges support from the Spanish Ministerio de Ciencia e Innovacion under contracts FIS2006-03376 and FIS2009-09895. A. Ankiewicz and N. Akhmediev acknowledge the support of the Australian Research Council (ARC) (Discovery Project DP0985394).
Modelling waterfowl abundance and distribution to inform conservation planning in Canada

Detailed knowledge of waterfowl abundance and distribution across Canada is lacking, which limits our ability to effectively conserve and manage their populations. We used 15 years of data from an aerial transect survey to model the abundance of 17 species or species groups of ducks within southern and boreal Canada. We included 78 climatic, hydrological, and landscape variables in Boosted Regression Tree models, allowing flexible response curves and multiway interactions among variables. We assessed predictive performance of the models using four metrics and calculated uncertainty as the coefficient of variation of predictions across 20 replicate models. Maps of predicted relative abundance were generated from resulting models, and they largely match spatial patterns evident in the transect data. We observed two main distribution patterns: a concentrated prairie-parkland distribution and a more dispersed pan-Canadian distribution. These patterns were congruent with the relative importance of predictor variables and model evaluation statistics among the two groups of distributions. Most species had a hydrological variable as the most important predictor, although the specific hydrological variable differed somewhat among species. In some cases, important variables had clear ecological interpretations, but in some instances, e.g., topographic roughness, they may simply reflect chance correlations between species distributions and environmental variables identified by the model-building process. Given the performance of our models, we suggest that the resulting prediction maps can be used in future research and to guide conservation activities, particularly within the bounds of the
Value of quantitative D-dimer assays in identifying pulmonary embolism: implications from a sequential decision model.

OBJECTIVES To examine the cost-effectiveness of a quantitative D-dimer assay for the evaluation of patients with suspected pulmonary embolism (PE) in an urban emergency department (ED). METHODS The authors analyzed different diagnostic strategies over pretest risk categories on the basis of Wells criteria by using the performance profile of the ELISA D-dimer assay (over five cutoff values) and imaging strategies used in the ED for PE: compression ultrasound (CUS), ventilation-perfusion (VQ) scan (over three cutoff values), CUS with VQ (over three cutoff values), computed tomography (CT) angiogram (CTA) with pulmonary portion (CTP) and lower-extremity venous portion, and CUS with CTP. Data used in the analysis were based on literature review. Incremental costs and quality-adjusted-life-years were the outcomes measured. RESULTS Computed tomography angiogram with pulmonary portion and lower-extremity venous portion without D-dimer was the preferred strategy. CUS-VQ scanning always was dominated by CT-based strategies. When CTA was infeasible, the dominant strategy was D-dimer with CUS-VQ in moderate- and high-Wells patients and was D-dimer with CUS for low-Wells patients. When CTP specificity falls below 80%, or if its overall performance is markedly degraded, preferred strategies include D-dimer testing. Sensitivity analyses suggest that pessimistic assessments of CTP accuracy alter the results only at extremes of parameter settings. CONCLUSIONS In patients in whom PE is suspected, when CTA is available, even the most sensitive quantitative D-dimer assay is not likely to be cost-effective. When CTA is not available or if its performance is markedly degraded, use of the D-dimer assay has value in combination with CUS and a pulmonary imaging study. These conclusions may not hold for the larger domain of patients presenting to the ED with chest pain or shortness of breath in whom PE is one of many competing diagnoses.
Frequency, heterogeneity and encephalitogenicity of T cells specific for myelin oligodendrocyte glycoprotein in naive outbred primates

Auto‐reactive T cells present in healthy subjects remain in a state of unresponsiveness, but may trigger autoimmunity under various situations. Although myelin oligodendrocyte glycoprotein (MOG) is a potential target antigen in multiple sclerosis (MS), MOG‐reactive T cell responses are present in the blood of both healthy subjects and MS‐affected individuals. To investigate the disease‐inducing potential and regulation of these autoreactive T cells in healthy outbred populations, we have characterized MOG‐reactive T cell clones obtained by limiting dilution from peripheral blood ofunimmunized C. jacchus marmosets. We report an extraordinarily high prevalence of circulating MOG‐reactive T cells in these naive animals (2.6 ± 1.4 / 105 PBMC), and a broadly diverse repertoire of epitope recognition encompassing at least three regions within the extracellular domain of MOG. Adoptive transfer of a MOG21 – 40‐specific T cell clone resulted in mild clinical experimental allergic encephalomyelitis, characterized pathologically by rare foci of inflammation and minimal demyelination. We conclude that MOG‐reactive T cells are present in healthy primates at a highly prevalent frequency, and are potentially capable of triggering central nervous system autoimmunity. Expansion of these autoreactive T cells must be tightly controlled to maintain immune homeostasis in healthy individuals.
Isolation and Cloning of Multipotential Stem Cells from the Embryonic Human CNS and Establishment of Transplantable Human Neural Stem Cell Lines by Epigenetic Stimulation

Stem cells that can give rise to neurons, astroglia, and oligodendroglia have been found in the developing and adult central nervous system (CNS) of rodents. Yet, their existence within the human brain has not been documented, and the isolation and characterization of multipotent embryonic human neural stem cells have proven difficult to accomplish. We show that the developing human CNS embodies multipotent precursors that differ from their murine counterpart in that they require simultaneous, synergistic stimulation by both epidermal and fibroblast growth factor-2 to exhibit critical stem cell characteristics. Clonal analysis demonstrates that human C NS stem cells are multipotent and differentiate spontaneously into neurons, astrocytes, and oligodendrocytes when growth factors are removed. Subcloning and population analysis show their extensive self-renewal capacity and functional stability, their ability to maintain a steady growth profile, their multipotency, and a constant potential for neuronal differentiation for more than 2 years. The neurons generated by human stem cells over this period of time are electrophysiologically active. These cells are also cryopreservable. Finally, we demonstrate that the neuronal and glial progeny of long-term cultured human CNS stem cells can effectively survive transplantation into the lesioned striatum of adult rats. Tumor formation is not observed, even in immunodeficient hosts. Hence, as a consequence of their inherent biology, human CNS stem cells can establish stable, transplantable cell lines by epigenetic stimulation. These lines represent a renewable source of neurons and glia and may significantly facilitate research on human neurogenesis and the development of clinical neural transplantation.
Residential exposure to fine particulate matter air pollution and incident breast cancer in a cohort of Canadian women

Background: Air pollution has been classified as a human carcinogen based largely on epidemiological studies of lung cancer. Recent research suggests that exposure to ambient air pollution increases the risk of breast cancer. Methods: Our aim was to characterize associations between residential exposure to ambient fine particulate matter (PM2.5) and the incidence of breast cancer in a cohort of 89,247 women enrolled in the Canadian National Breast Screening Study between 1980 and 1985. Vital status and incident cancers were determined through record linkage to the national registry data through 2005. Individual-level estimates of exposures to PM2.5 at baseline were derived from satellite observations. Six thousand five hundred three incident breast cancers were identified during follow-up. We classified menopausal status using self-reported information collected at baseline and by attained age (50, 52, and 54 years) as women were followed-up. We computed hazard ratios (HRs) and their 95% confidence intervals (CI) using age as the time axis. Models were adjusted for several individual risk factors, including reproductive history, as well as census-based neighborhood-level characteristics. Results: The median residential concentration of PM2.5 was 9.1 &mgr;g/m3. In models adjusted for personal and contextual risk factors, a 10-&mgr;g/m3 increase in PM2.5 was associated with an elevated risk of premenopausal (HR = 1.26; 95% CI = 0.99, 1.61) but not postmenopausal breast cancer (HR = 1.01; 95% CI = 0.94, 1.10). The elevated risk of premenopausal breast cancer from PM2.5 was only evident among those randomized to the screening arm of the study. Conclusions: Our findings support the hypothesis that exposure to low concentrations of PM2.5 increase the risk of premenopausal breast cancer.