Miracle-dz/UniFAR-FTUs huggingface dataset:
Highly Precise and Developmentally Programmed Genome Assembly in Paramecium Requires Ligase IV–Dependent End Joining

During the sexual cycle of the ciliate Paramecium, assembly of the somatic genome includes the precise excision of tens of thousands of short, non-coding germline sequences (Internal Eliminated Sequences or IESs), each one flanked by two TA dinucleotides. It has been reported previously that these genome rearrangements are initiated by the introduction of developmentally programmed DNA double-strand breaks (DSBs), which depend on the domesticated transposase PiggyMac. These DSBs all exhibit a characteristic geometry, with 4-base 5′ overhangs centered on the conserved TA, and may readily align and undergo ligation with minimal processing. However, the molecular steps and actors involved in the final and precise assembly of somatic genes have remained unknown. We demonstrate here that Ligase IV and Xrcc4p, core components of the non-homologous end-joining pathway (NHEJ), are required both for the repair of IES excision sites and for the circularization of excised IESs. The transcription of LIG4 and XRCC4 is induced early during the sexual cycle and a Lig4p-GFP fusion protein accumulates in the developing somatic nucleus by the time IES excision takes place. RNAi–mediated silencing of either gene results in the persistence of free broken DNA ends, apparently protected against extensive resection. At the nucleotide level, controlled removal of the 5′-terminal nucleotide occurs normally in LIG4-silenced cells, while nucleotide addition to the 3′ ends of the breaks is blocked, together with the final joining step, indicative of a coupling between NHEJ polymerase and ligase activities. Taken together, our data indicate that IES excision is a “cut-and-close” mechanism, which involves the introduction of initiating double-strand cleavages at both ends of each IES, followed by DSB repair via highly precise end joining. This work broadens our current view on how the cellular NHEJ pathway has cooperated with domesticated transposases for the emergence of new mechanisms involved in genome dynamics.
Current Perspectives on the Use of Alternative Species in Human Health and Ecological Hazard Assessments

Background: Traditional animal toxicity tests can be time and resource intensive, thereby limiting the number of chemicals that can be comprehensively tested for potential hazards to humans and/or to the environment. Objective: We compared several types of data to demonstrate how alternative models can be used to inform both human and ecological risk assessment. Methods: We reviewed and compared data derived from high throughput in vitro assays to fish reproductive tests for seven chemicals. We investigated whether human-focused assays can be predictive of chemical hazards in the environment. We examined how conserved pathways enable the use of nonmammalian models, such as fathead minnow, zebrafish, and Xenopus laevis, to understand modes of action and to screen for chemical risks to humans. Results: We examined how dose-dependent responses of zebrafish embryos exposed to flusilazole can be extrapolated, using pathway point of departure data and reverse toxicokinetics, to obtain human oral dose hazard values that are similar to published mammalian chronic toxicity values for the chemical. We also examined how development/safety data for human health can be used to help assess potential risks of pharmaceuticals to nontarget species in the environment. Discussion: Using several examples, we demonstrate that pathway-based analysis of chemical effects provides new opportunities to use alternative models (nonmammalian species, in vitro tests) to support decision making while reducing animal use and associated costs. Conclusions: These analyses and examples demonstrate how alternative models can be used to reduce cost and animal use while being protective of both human and ecological health. Citation: Perkins EJ, Ankley GT, Crofton KM, Garcia-Reyero N, LaLone CA, Johnson MS, Tietge JE, Villeneuve DL. 2013. Current perspectives on the use of alternative species in human health and ecological hazard assessments. Environ Health Perspect 121:1002–1010; http://dx.doi. org/10.1289/ehp.1306638
Is There a Future for Small Hospitals in Germany?

We analyse the financial performance of small German hospitals based on balance sheet data of about 1,000 hospitals in 2007. Measures of financial performance are the earnings before interest, tax, depreciation, and amortisation (EBITDA) and the probability of default (PD). We find that, on average, small hospitals have more financial difficulties than large ones. However, there is considerable heterogeneity among small hospitals. While small private-for-profit hospitals tend to perform very well, small public hospitals face considerable financial problems. Apart from ownership, we find that specialisation, less subsidies in absolute terms, and a higher share of lump-sum subsidies are associated with a better financial performance.
Comparison of the Damaged Area Caused by an Agricultural Dam-Break Flood Wave Using HEC-RAS and UAV Surveying

This study examines the usability of unmanned aerial vehicle (UAV) data surveyed just after an agricultural reservoir collapse by comparing the survey results with the simulation results of the HEC-RAS (Hydrologic Engineering Centers River Analysis System) flood wave propagation to the downstream areas. A 61,400 m3 storage dam broken by 89.0 mm (over 30.0 mm/hr rainfall intensity) of rainfall on August 21st, 2014 was considered. The reservoir water capacity curve and downstream damaged areas were estimated by drone surveying 3 days after the dam break. The flood wave by the overtopped dam break was propagated using the HEC-HMS (Hydrologic Engineering Centers Hydrological Modeling System) reservoir inflow from the watershed. The model results showed flood inundation depths of 0.1 to 2.2 m, mainly in rice paddy areas along the stream, and the overtopped dam-break scenario exhibited 59% correspondence with the drone-surveyed areas.
The (Ir)Relevance of Real Wage Rigidity in the New Keynesian Model with Search Frictions

We explore the role of real wage dynamics in a New Keynesian business cycle model with search and matching frictions in the labor market. Both job creation and destruction are endogenous. We show that the model generates counterfactual inflation and labor market dynamics. In particular, it fails to generate a Beveridge curve: vacancies and unemployment are positively correlated. Introducing real wage rigidity leads to a negative correlation, and increases the magnitude of labor market flows to more realistic values. However, inflation dynamics are only weakly affected by real wage rigidity. This is because of the presence of labor market frictions, which generate long-run employment relationships. The measure of real marginal cost that is relevant for inflation dynamics via the Phillips curve contains a dynamic component that does not necessarily move with real wages.
Long term follow up of children with myocarditis treated by immunosuppression and of children with dilated cardiomyopathy

Objective: To describe the treatment and long term outcome after immunosuppressive treatment of children with myocarditis. Methods and results: 114 patients with newly diagnosed dilated cardiomyopathy were divided into three groups, according to the histological pattern: group A, acute myocarditis; group B, borderline myocarditis; and group C, non-inflammatory cardiomyopathy. Groups A and B were treated with cyclosporine and prednisone in addition to conventional treatment. Survivors of the whole cohort were analysed for 13 year transplant-free survival and assessed for left ventricular function. Event-free survival at 13 years was 97 (3)% for group A, 70 (8)% for group B, and 32 (7)% for group C (p < 0.0001). It was 96 (4)% at one year and 83 (5)% at 13 years for the cumulated myocarditis group (A and B). Cardiac function recovered completely in 79% of survivors in group A, 64% in group B, and 36% in group C. The rate of complete recovery in the cumulated group (A and B) was 70%. Conclusions: The high long term survival rate of this cohort of children with myocarditis is probably due to the effect of short term immunosuppression. This result differs from previously published series of conventionally treated children, whose survival probability at one year was about 60%.
Autonomous flight at low altitude with vision-based collision avoidance and GPS-based path following

The ability to fly at low altitude while actively avoiding collisions with the terrain and other objects is a great challenge for small unmanned aircraft. This paper builds on top of a control strategy called optiPilot whereby a series of optic-flow detectors pointed at divergent viewing directions around the aircraft main axis are linearly combined into roll and pitch commands using two sets of weights. This control strategy already proved successful at controlling flight and avoiding collisions in reactive navigation experiments. This paper shows how optiPilot can be coupled with a GPS in order to provide goal-directed, nap-of-the-earth flight control in presence of static obstacles. Two fully autonomous flights of 25 minutes each are described where a 400-gram unmanned aircraft is flying at approx. 9 m above the terrain on a circular path including two copses of trees requiring efficient collision avoidance actions.
Reducing the n-gram feature space of class C GPCRs to subtype-discriminating patterns

Summary G protein-coupled receptors (GPCRs) are a large and heterogeneous superfamily of receptors that are key cell players for their role as extracellular signal transmitters. Class C GPCRs, in particular, are of great interest in pharmacology. The lack of knowledge about their full 3-D structure prompts the use of their primary amino acid sequences for the construction of robust classifiers, capable of discriminating their different subtypes. In this paper, we investigate the use of feature selection techniques to build Support Vector Machine (SVM)-based classification models from selected receptor subsequences described as n-grams. We show that this approach to classification is useful for finding class C GPCR subtype-specific motifs.
Engineering the Redox Potential over a Wide Range within a New Class of FeS Proteins

MitoNEET is a newly discovered mitochondrial protein and a target of the TZD class of antidiabetes drugs. MitoNEET is homodimeric with each protomer binding a [2Fe-2S] center through a rare 3-Cys and 1-His coordination geometry. Both the fold and the coordination of the [2Fe-2S] centers suggest that it could have novel properties compared to other known [2Fe-2S] proteins. We tested the robustness of mitoNEET to mutation and the range over which the redox potential (EM) could be tuned. We found that the protein could tolerate an array of mutations that modified the EM of the [2Fe-2S] center over a range of ∼700 mV, which is the largest EM range engineered in an FeS protein and, importantly, spans the cellular redox range (+200 to −300 mV). These properties make mitoNEET potentially useful for both physiological studies and industrial applications as a stable, water-soluble, redox agent.
A preliminary comparison of tree encoding schemes for evolutionary algorithms

This paper presents a comparative study of six encodings which have been used to represent trees in evolutionary algorithms. The study has been divided into two steps: 1) The encoding methods have been evaluated taking into account the time necessary to perform operations such as decoding, crossover and mutation, the feasibility of solutions after those operations, and the corresponding heritability and locality; 2) The encoding methods have been employed in a genetic algorithm to solve three different instances (with 10, 25 and 50 nodes) of the optimal communication spanning tree problem. Finally, the results obtained with each of the encodings are statistically compared using Kruskal-Wallis non-parametric tests and multiple comparisons. The results of this study provide insight into the properties of current encoding schemes for network design problems.
Autocorrelation of cycle times in semiconductor manufacturing systems

Due to the high complexity of semiconductor manufacturing systems simulation has become a useful tool for the performance analysis of these systems. However, there are some serious problems in analyzing simulation output data. For example, the quality of confidence intervals for certain performance measures is affected by correlations among the data. Furthermore, analyzing the correlation of simulation output data might give valuable hints for understanding the behavior of complex systems such as semiconductor manufacturing systems. In this paper we present examples where we have detected remarkable correlation phenomena, in the simulation output of semiconductor fabrication facilities caused by exo- or endogenous factors. Based on real specifications we examine several semiconductor manufacturing systems in steady state. First we calculate the autocorrelation function of the sequence of successive cycle times and then compute the corresponding frequency spectrum. By this means, periodicities in the simulation output data can efficiently be determined.
Outcomes of Treated Human Granulocytic Ehrlichiosis Cases

We conducted a case-control study in Wisconsin to determine whether some patients have long-term adverse health outcomes after antibiotic treatment for human granulocytic ehrlichiosis (HGE). A standardized health status questionnaire was administered to patients and controls matched by age group and sex. Consenting patients provided blood samples for serologic testing. Among the 85 previously treated patients, the median interval since onset of illness was 24 months. Compared with 102 controls, patients were more likely to report recurrent or continuous fevers, chills, fatigue, and sweats. Patients had lower health status scores than controls for bodily pain and health relative to 1 year earlier, but there was no significant difference in physical functioning, role limitations, general health, or vitality measures. The HGE antibody titer remained elevated in one patient; two had elevated aspartate aminotransferase levels. HGE may cause a postinfectious syndrome characterized by constitutional symptoms without functional disability or serologic evidence of persistent infection.
Chemokine receptor 4 gene silencing blocks neuroblastoma metastasis in vitro

This study investigated the effects of small interfering RNA (siRNA)-mediated silencing of chemokine receptor 4 (CXCR4) on the invasion capacity of human neuroblastoma cell line SH-SY5Y in vitro. Three siRNAs targeting CXCR4 were chemically synthesized and individually transfected into SH-SY5Y cells. Expression of CXCR4 mRNA and protein was significantly suppressed in transfected cells by all three sequence-specific siRNAs compared with control groups. Furthermore, the invasion capacity of SH-SY5Y cells was significantly decreased following transfection with CXCR4-specific siRNA compared with the control groups. These data demonstrate that down-regulation of CXCR4 can inhibit in vitro invasion of neuroblastoma.
Dissociated Dipoles: Image Representation via Non-local Comparisons

Abstract : A fundamental question in visual neuroscience is how to represent image structure. The most common representational schemes rely on differential operators that compare adjacent image regions. While well-suited to encoding local relationships, such operators have significant drawbacks. Specifically, each filter's span is confounded with the size of its sub-fields, making it difficult to compare small regions across large distances. We find that such long-distance comparisons are more tolerant to common image transformations than purely local ones, suggesting they may provide a useful vocabulary for image encoding. We introduce the Dissociated Dipole, or Sticks operator, for encoding non-local image relationships. This operator de-couples filter span from sub-field size, enabling parametric movement between edge and region-based representation modes. We report on the perceptual plausibility of the operator, and the computational advantages of non-local encoding. Our results suggest that non-local encoding may be an effective scheme for representing image structure.
TCP performance over multipath routing in mobile ad hoc networks

In this paper, we investigate TCP performance over a multipath routing protocol. Multipath routing can improve the path availability in mobile environment. Thus, it has a great potential to improve TCP performance in ad hoc networks under mobility. Previous research on multipath routing mostly used UDP traffic for performance evaluation. When TCP is used, we find that most times, using multiple paths simultaneously may actually degrade TCP performance. This is partly due to frequent out-of-order packet delivery via different paths. We then test another multipath routing strategy called backup path routing. Under the backup path routing scheme, TCP is able to gain improvements against mobility. We then further study related issues to backup path routing, which can affect TCP performance. Some important discoveries are reported in the paper and simulation results show that by careful selection of the multipath routing strategies, we can improve TCP performance by more than 30% even under very high mobility.
Laboratory studies on the bearing capacity of unsaturated sands

In this thesis, extensive experimental studies were undertaken by conducting more than 250 bearing capacity tests on model footings to investigate the bearing capacity of three compacted (coarse-grained, sub-coarse-grained, and fine-grained) sands under both saturated and unsaturated conditions. These tests were conducted in specially designed equipment which includes two test systems for conducting bearing capacity tests using model footings. The designed equipment system had provisions for soil drainage, soil suction profile set for measuring the variation of matric suction with depth of water table, tensiometer holders, vacuum water pumps and other accessories. Two different soil containers (short container with 300 mm in diameter and 300 mm in height and the tall container with 300 mm in diameter and 700 mm in height) were used in the study. The bearing capacity was determined using four different sizes of square model footings (i.e. 20 mm x 20 mm, 25 mm x 25 mm, 37.5 mm x 37.5 mm, and 50 mm x 50 mm). All the equipment was designed by the author and fabricated in the student workshop at University of Ottawa. The experimental results demonstrated that the bearing capacity of unsaturated fine-grained sand increases as the matric suction increases. However, experimental studies on coarse-grained sand show that bearing capacity appears to decrease as the matric suction increases. Some practical reasons for such a behavior are explained in the thesis. Experimental studies have also demonstrated that footing sizes in the range of 20 mm x 20 mm to 150 mm x 150 mm had no significant influence on the bearing capacity of sandy soils. The boundary conditions (i.e., ratio of soil container size to footing size) have some effect on the bearing capacity of sands. A separate experimental program Saturated compacted silt after settlement offers significant resistance to the applied static loads without undergoing creep, however; bearing capacity reduces significantly when it is subjected to dynamic or cyclic loading conditions.
Isoflavone Pharmacokinetics and Metabolism after Consumption of a Standardized Soy and Soy–Almond Bread in Men with Asymptomatic Prostate Cancer

Epidemiologic associations suggest that populations consuming substantial amounts of dietary soy exhibit a lower risk of prostate cancer. A 20-week randomized, phase II, crossover trial was conducted in 32 men with asymptomatic prostate cancer. The crossover involved 8 weeks each of soy bread (SB) and soy–almond bread (SAB). The primary objective was to investigate isoflavone bioavailability and metabolite profile. Secondary objectives include safety, compliance, and assessment of biomarkers linked to prostate carcinogenesis. Two distinct SBs were formulated to deliver approximately 60 mg aglycone equivalents of isoflavones per day. The isoflavones were present as aglycones (∼78% as aglycones) in the SAB whereas in the standard SB predominantly as glucosides (18% total isoflavones as aglycones). Compliance to SB (97% ± 4%) and SAB (92% ± 18%) was excellent; toxicity was rare and limited to grade 1 gastrointestinal complaints. Pharmacokinetic studies between SB and SAB showed modest differences. Peak serum concentration time (Tmax) was significantly faster with SAB meal compared with SB in some isoflavonoids, and AUC0 to 24 h of dihydrodaidzein and O-desmethylangolensin was significantly greater after an SB meal. An exploratory cluster analysis was used to identify four isoflavone-metabolizing phenotypes. Insulin-like growth factor–binding protein increased significantly by 41% (P = 0.024) with soy intervention. Findings from this study provide the necessary framework to study isoflavone-metabolizing phenotypes as a strategy for identification of individuals that might benefit or show resistance to cancer preventive strategies using dietary soy. A standardized SB used for future large-scale randomized clinical trials to affect human prostate carcinogenesis is feasible. Cancer Prev Res; 8(11); 1045–54. ©2015 AACR.
Optimization of Dual-Speed TAM Architectures for Efficient Modular Testing of SOCs

The increasing complexity of system-on-chip (SOC) integrated circuits has spurred the development of versatile automatic test equipment (ATE) that can simultaneously drive different channels at different data rates. Examples of such ATEs include the Agilent 93000 series tester based on port scalability and the test processor-per-pin architecture and the Tiger system from Teradyne. The number of tester channels with high data rates may be constrained in practice, however, due to ATE resource limitations, the power rating of the SOC, and scan frequency limits for the embedded cores. Therefore, we formulate the following optimization problem: Given two available data rates for the tester channels, an SOC-level test access mechanism (TAM) width W, an upper limit V (V<W) on the number of channels that can transport test data at the higher data rate, determine an SOC TAM architecture that minimizes the testing time. We present an efficient heuristic algorithm for TAM optimization that exploits port scalability of ATEs to reduce SOC testing time and test cost. We present experimental results for the ITC '02 SOC test benchmarks and investigate the impact of dual-speed TAM architectures on power consumption during testing for one of these benchmarks
How Easy is Matching 2D Line Models Using Local Search?

Local search is a well established and highly effective method for solving complex combinatorial optimization problems. Here, local search is adapted to solve difficult geometric matching problems. Matching is posed as the problem of finding the optimal many-to-many correspondence mapping between a line segment model and image line segments. Image data is assumed to be fragmented, noisy, and cluttered. The algorithms presented have been used for robot navigation, photo interpretation, and scene understanding. This paper explores how local search performs as model complexity increases, image clutter increases, and additional model instances are added to the image data. Expected run-times to find optimal matches with 95 percent confidence are determined for 48 distinct problems involving six models. Nonlinear regression is used to estimate run-time growth as a function of problem size. Both polynomial and exponential growth models are fit to the run-time data. For problems with random clutter, the polynomial model fits better and growth is comparable to that for tree search. For problems involving symmetric models and multiple model instances, where tree search is exponential, the polynomial growth model is superior to the exponential growth model for one search algorithm and comparable for another.