Miracle-dz/UniFAR-FTUs huggingface dataset:
The Yeast Trimeric Guanine Nucleotide-Binding Protein α Subunit, Gpa2p, Controls the Meiosis-Specific Kinase Ime2p Activity in Response to Nutrients

ABSTRACT Saccharomyces cerevisiae Gpa2p, the α subunit of a heterotrimeric guanine nucleotide-binding protein (G protein), is involved in the regulation of vegetative growth and pseudohyphal development. Here we report that Gpa2p also controls sporulation by interacting with the regulatory domain of Ime2p (Sme1p), a protein kinase essential for entrance of meiosis and sporulation. Protein-protein interactions between Gpa2p and Ime2p depend on the GTP-bound state of Gpa2p and correlate with down-regulation of Ime2p kinase activity in vitro. Overexpression of Ime2p inhibits pseudohyphal development and enables diploid cells to sporulate even in the presence of glucose or nitrogen. In contrast, overexpression of Gpa2p in cells simultaneously overproducing Ime2p results in a drastic reduction of sporulation efficiency, demonstrating an inhibitory effect of Gpa2p on Ime2p function. Furthermore, deletion of GPA2 accelerates sporulation on low-nitrogen medium. These observations are consistent with the following model. In glucose-containing medium, diploid cells do not sporulate because Ime2p is inactive or expressed at low levels. Upon starvation, expression of Gpa2p and Ime2p is induced but sporulation is prevented as long as nitrogen is present in the medium. The negative control of Ime2p kinase activity is exerted at least in part through the activated form of Gpa2p and is released as soon as nutrients are exhausted. This model attributes a switch function to Gpa2p in the meiosis-pseudohyphal growth decision.
Integrating autonomous behavior and user control for believable agents

Autonomous agents can help users by taking on a substantial workload, and performing tasks that are too complex for a human. However, in some systems complete autonomy is undesirable as it removes control from the user. It is therefore important to include some user control while maintaining the reduced workload associated with an autonomous system. This is particularly true of user avatars in virtual worlds, appropriate non-verbal communication is too complex to be directed explicitly and should therefore be controlled by an agent. However, the non-verbal communication should express the feelings of the user, so a degree of human input is needed. This paper presents Demeanour, an autonomous system for generating body language in avatars, which integrates user input based on a three level methodology of customization and control.
Analysis of 14 LRRK2 mutations in Parkinson's plus syndromes and late‐onset Parkinson's disease

The pleomorphic pathology of postmortem LRRK2‐positive patients and the frequent association with late‐onset Parkinson's disease (LOPD) symptoms suggest that LRRK2 mutations may play a role in Parkinson's Plus disorders and LOPD. Published studies primarily focus on the common G2019S mutation. Analysis of a spectrum of LRRK2 mutations in Parkinson's Plus disorders has yet to be reported. We investigated 14 leucine‐rich repeat kinase 2 (LRRK2) mutations in a cohort of Parkinson's Plus disorders and LOPD. A total of 458 patients with progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal ganglionic degeneration (CBGD), atypical Parkinsonism (AP), and LOPD were screened for 14 mutations that span exons 19 to 41 of the LRRK2 gene. Among the LOPD cases, 1 patient was found to harbor the R1441C mutation. He presented with typical features of PD at age of 58 years old and responded well to levodopa. We did not detect any of the 14 mutations in PSP, MSA, CBGD, and AP patients. We highlight the first case of LRRK2 R1441C mutation in late onset sporadic PD of non‐European ancestry. Furthermore, extensive mutational screen found LRRK2 mutations to be rare among patients who presented with PSP, MSA, CBGD, and AP. © 2006 Movement Disorder Society
Negative Correlation between Individual-Insect-Level Virulence and Colony-Level Virulence of Paenibacillus larvae, the Etiological Agent of American Foulbrood of Honeybees

ABSTRACT Paenibacillus larvae is the etiological agent of American foulbrood (AFB) in honeybees. Recently, different genotypes of P. larvae (ERIC I to ERIC IV) were defined, and it was shown that these genotypes differ inter alia in their virulence on the larval level. On the colony level, bees mitigate AFB through the hygienic behavior of nurse bees. Therefore, we investigated how the hygienic behavior shapes P. larvae virulence on the colony level. Our results indicate that P. larvae virulence on the larval level and that on the colony level are negatively correlated.
Impact of Freezing Delay Time on Tissue Samples for Metabolomic Studies

Introduction Metabolic profiling of intact tumor tissue by high-resolution magic angle spinning (HR MAS) MR spectroscopy (MRS) provides important biological information possibly useful for clinical diagnosis and development of novel treatment strategies. However, generation of high-quality data requires that sample handling from surgical resection until analysis is performed using systematically validated procedures. In this study, we investigated the effect of postsurgical freezing delay time on global metabolic profiles and stability of individual metabolites in intact tumor tissue. Materials and methods Tumor tissue samples collected from two patient-derived breast cancer xenograft models (n = 3 for each model) were divided into pieces that were snap-frozen in liquid nitrogen at 0, 15, 30, 60, 90, and 120 min after surgical removal. In addition, one sample was analyzed immediately, representing the metabolic profile of fresh tissue exposed neither to liquid nitrogen nor to room temperature. We also evaluated the metabolic effect of prolonged spinning during the HR MAS experiments in biopsies from breast cancer patients (n = 14). All samples were analyzed by proton HR MAS MRS on a Bruker Avance DRX600 spectrometer, and changes in metabolic profiles were evaluated using multivariate analysis and linear mixed modeling. Results Multivariate analysis showed that the metabolic differences between the two breast cancer models were more prominent than variation caused by freezing delay time. No significant changes in levels of individual metabolites were observed in samples frozen within 30 min of resection. After this time point, levels of choline increased, whereas ascorbate, creatine, and glutathione (GS) levels decreased. Freezing had a significant effect on several metabolites but is an essential procedure for research and biobank purposes. Furthermore, four metabolites (glucose, glycine, glycerophosphocholine, and choline) were affected by prolonged HR MAS experiment time possibly caused by physical release of metabolites caused by spinning or due to structural degradation processes. Conclusion The MR metabolic profiles of tumor samples are reproducible and robust to variation in postsurgical freezing delay up to 30 min.
On the stratified dust distribution of the GG Tauri circumbinary ring

Aims. Our objective is to study the vertical dust distribution in the circumbinary ring of the binary system GG Tau and to search for evidence of stratification, one of the first steps expected to occur during planet formation. Methods. We present a simultaneous analysis of four scattered light images spanning a range of wavelength from 800 nm to 3600 nm and compare them with (i) a parametric prescription for the vertical dust stratification, and (ii) with the results of SPH bi-fluid hydrodynamic calculations. Results. The parametric prescription and hydrodynamical calculations of stratification both reproduce the observed brightness profiles well. These models also provide a correct match for the observed star/ring integrated flux ratio. Another solution with a well-mixed, but “exotic”, dust size distribution also matches the brightness profile ratios but fails to match the star/ring flux ratio. These results give support to the presence of vertical stratification of the dust in the ring of GG Tau and also allow us to predict the presence of a radial stratification.
Mechanism of West Nile Virus Neuroinvasion: A Critical Appraisal

West Nile virus (WNV) is an important emerging neurotropic virus, responsible for increasingly severe encephalitis outbreaks in humans and horses worldwide. However, the mechanism by which the virus gains entry to the brain (neuroinvasion) remains poorly understood. Hypotheses of hematogenous and transneural entry have been proposed for WNV neuroinvasion, which revolve mainly around the concepts of blood-brain barrier (BBB) disruption and retrograde axonal transport, respectively. However, an over‑representation of in vitro studies without adequate in vivo validation continues to obscure our understanding of the mechanism(s). Furthermore, WNV infection in the current rodent models does not generate a similar viremia and character of CNS infection, as seen in the common target hosts, humans and horses. These differences ultimately question the applicability of rodent models for pathogenesis investigations. Finally, the role of several barriers against CNS insults, such as the blood-cerebrospinal fluid (CSF), the CSF-brain and the blood-spinal cord barriers, remain largely unexplored, highlighting the infancy of this field. In this review, a systematic and critical appraisal of the current evidence relevant to the possible mechanism(s) of WNV neuroinvasion is conducted.
A Method for the Time-Varying Nonlinear Prediction of Complex Nonstationary Biomedical Signals

A method to perform time-varying (TV) nonlinear prediction of biomedical signals in the presence of nonstationarity is presented in this paper. The method is based on identification of TV autoregressive models through expansion of the TV coefficients onto a set of basis functions and on k -nearest neighbor local linear approximation to perform nonlinear prediction. The approach provides reasonable nonlinear prediction even for TV deterministic chaotic signals, which has been a daunting task to date. Moreover, the method is used in conjunction with a TV surrogate method to provide statistical validation that the presence of nonlinearity is not due to nonstationarity itself. The approach is tested on simulated linear and nonlinear signals reproducing both time-invariant (TIV) and TV dynamics to assess its ability to quantify TIV and TV degrees of predictability and detect nonlinearity. Applicative examples relevant to heart rate variability and EEG analyses are then illustrated.
Dual Range Deringing for non-blind image deconvolution

The popular Richardson-Lucy (RL) image deconvolution algorithm often produces undesirable ringing artifacts. In this paper, we propose a novel Dual Range Deringing (DRD) algorithm to address this problem. As a post-deconvolution scheme, the proposed approach follows RL deconvolution and removes ringing artifacts by utilizing information from both the input blurred image and the RL-deblurred image. DRD first marks smooth regions in the input blurred image that are likely to be subjected to ringing artifacts far away from any strong edge. It then identifies short-range ringing artifacts from the regions that surround strong edges in the RL-deblurred image. Once marked, both long- and short-range ringing artifacts are then suppressed by an edgepreserving deringing filter. We demonstrate the effectiveness of this procedure by performing experiments on a set of images blurred with various Point Spread Functions (PSFs). We compare DRD with state-of-the-art non-blind deconvolution algorithms and show that our results are virtually free of ringing artifacts with only minor detail losses. Moreover, DRD consists of computationally efficient local operations and is suitable for parallelization on modern GPUs.
Mining Frequent Trajectory Patterns for Activity Monitoring Using Radio Frequency Tag Arrays

Activity monitoring, a crucial task in many applications, is often conducted expensively using video cameras. Effectively monitoring a large field by analyzing images from multiple cameras remains a challenging issue. Other approaches generally require the tracking objects to attach special devices, which are infeasible in many scenarios. To address the issue, we propose to use RF tag arrays for activity monitoring, where data mining techniques play a critical role. The RFID technology provides an economically attractive solution due to the low cost of RF tags and readers. Another novelty of this design is that the tracking objects do not need to be equipped with any RF transmitters or receivers. By developing a practical fault-tolerant method, we offset the noise of RF tag data and mine frequent trajectory patterns as models of regular activities. Our empirical study using real RFID systems and data sets verifies the feasibility and the effectiveness of this design.
General practitioners and doping in sport: attitudes and experience

Objectives: To examine the attitudes to, and knowledge of, doping in sport of French general practitioners (GPs), and their contact with drug taking athletes on an everyday basis. Methods: A total of 402 GPs were randomly selected from all over France and interviewed by telephone, using a prepared script. Results: The response rate was 50.5% (153 men and 49 women; mean (SD) age 45.6 (5.6) years). Of the respondents, 73% confirmed that they had the list of banned products, and only 34.5% stated that they were aware of the latest French law, brought into effect in March 1999, concerning the fight against doping. Some 11% had directly encountered a request for prescription of doping agents over the preceding 12 months (the requested substances were mainly anabolic steroids, stimulants, and corticosteroids), and 10% had been consulted by an athlete who was using doping drugs and was frightened of the health risks (the substances used were mainly anabolic steroids). Over half (52%) of the GPs favoured the prescription of drug substitutions to athletes who used doping agents. According to 87.5% of respondents, doping is a public health problem, and 80% stated that doping is a form of drug addiction. Most (89%) said that a GP has a role to play in doping prevention, but 77% considered themselves poorly prepared to participate in its prevention. Conclusion: The results suggest that (a) GPs have limited knowledge of doping and (b) are confronted with doping in their daily practice, at least occasionally.
An Integer Sequence Motivated by Generalized Quadrangles

In this paper, we prove a closed form for a sequence motivated by the search for new generalized quadrangles of odd order. We present two proofs: a direct proof to explain the closed form’s derivation and a shorter inductive argument. The sequence in question is derived from congruences that arise from applying the Hermite-Dickson criterion to a permutation polynomial that is related to the girth of monomial graphs.
Evaluating Las Vegas Algorithms: Pitfalls and Remedies

Stochastic search algorithms are among the most sucessful approaches for solving hard combinatorial problems. A large class of stochastic search approaches can be cast into the framework of Las Vegas Algorithms (LVAs). As the run-time behavior of LVAs is characterized by random variables, the detailed knowledge of run-time distributions provides important information for the analysis of these algorithms. In this paper we propose a novel methodology for evaluating the performance of LVAs, based on the identification of empirical run-time distributions. We exemplify our approach by applying it to Stochastic Local Search (SLS) algorithms for the satisfiability problem (SAT) in propositional logic. We point out pitfalls arising from the use of improper empirical methods and discuss the benefits of the proposed methodology for evaluating and comparing LVAs.
Expression of blaA Underlies Unexpected Ampicillin-Induced Cell Lysis of Shewanella oneidensis

Shewanella oneidensis is a facultative anaerobic γ-proteobacterium possessing remarkably diverse respiratory capacities for reducing various organic and inorganic substrates. As a veteran research model for investigating redox transformations of environmental contaminants the bacterium is well known to be a naturally ampicillin-resistant microorganism. However, in this study we discovered that ampicillin has a significant impact on growth of S. oneidensis. Particularly, cell lysis occurred only with ampicillin at levels ranging from 0.49 to 6.25 µg/ml but not at 50 µg/ml. This phenotype is attributable to insufficient expression of the β-lactamase BlaA. The subsequent analysis revealed that the blaA gene is strongly induced by ampicillin at high (50 µg/ml), but not at low levels (2.5 µg/ml). In addition, we demonstrated that penicillin binding protein 5 (PBP5), the most abundant low molecular weight PBP (LMW PBP), is the only one relevant to β-lactam resistance under the tested conditions. This nonessential PBP, largely resembling its Escherichia coli counterpart in functionality, mediates expression of the blaA gene.
Efficient flow profiling for detecting performance bugs

Performance issues in large applications arise only in particular scenarios under heavy load conditions. It is therefore difficult to catch them during testing and they easily escape into production. This necessitates the design of a common and efficient instrumentation strategy that profiles the flow of objects during an execution. Designing such a strategy which enables profile generation precisely with low overhead is non-trivial due to the number of objects created, accessed and paths traversed by them in an execution. In this paper, we design and implement an efficient instrumentation technique that efficiently generates object flow profiles for Java programs, without requiring any modifications to the underlying virtual machine. We achieve this by applying Ball-Larus numbering on a specialized hybrid flow graph (hfg). The hfg path profiles that are collected during runtime are post-processed offline to derive the object flow profiles. We implemented the profiler and validated its efficacy by applying it on Java programs. The results demonstrate the scalability of our approach, which handles 0.2M to 0.55B object accesses with an average runtime overhead of 8x. We also demonstrate the effectiveness of the generated profiles by implementing a client analysis that consumes the profiles to detect performance bugs. The analysis detects 38 performance bugs which when refactored result in significant performance gains (up to 30%) in running times.
Selection of an optimal antiseptic solution for intraoperative irrigation: an in vitro study.

BACKGROUND With increasing bacterial antibiotic resistance and an increased infection risk due to more complicated surgical procedures and patient populations, prevention of surgical infection is of paramount importance. Intraoperative irrigation with an antiseptic solution could provide an effective way to reduce postoperative infection rates. Although numerous studies have been conducted on the bactericidal or cytotoxic characteristics of antiseptics, the combination of these characteristics for intraoperative application has not been addressed. METHODS Bacteria (Staphylococcus aureus and S. epidermidis) and human cells were exposed to polyhexanide, hydrogen peroxide, octenidine dihydrochloride, povidone-iodine, and chlorhexidine digluconate at various dilutions for two minutes. Bactericidal properties were calculated by means of the quantitative suspension method. The cytotoxic effect on human fibroblasts and mesenchymal stromal cells was determined by a WST-1 metabolic activity assay. RESULTS All of the antiseptics except for polyhexanide were bactericidal and cytotoxic at the commercially available concentrations. When diluted, only povidone-iodine was bactericidal at a concentration at which some cell viability remained. The other antiseptics tested showed no cellular survival at the minimal bactericidal concentration. CONCLUSIONS Povidone-iodine diluted to a concentration of 1.3 g/L could be the optimal antiseptic for intraoperative irrigation. This should be established by future clinical studies.
Algorithms for Omega-Regular Games with Imperfect Information

We study observation-based strategies for two-player turn-based games on graphs with omega-regular objectives. An observation-based strategy relies on imperfect information about the history of a play, namely, on the past sequence of observations. Such games occur in the synthesis of a controller that does not see the private state of the plant. Our main results are twofold. First, we give a fixed-point algorithm for computing the set of states from which a player can win with a deterministic observation-based strategy for any omega-regular objective. The fixed point is computed in the lattice of antichains of state sets. This algorithm has the advantages of being directed by the objective and of avoiding an explicit subset construction on the game graph. Second, we give an algorithm for computing the set of states from which a player can win with probability 1 with a randomized observation-based strategy for a Buechi objective. This set is of interest because in the absence of perfect information, randomized strategies are more powerful than deterministic ones. We show that our algorithms are optimal by proving matching lower bounds.
Activation of c-Ha-Ras by Nitric Oxide Modulates Survival Responsiveness in Neuronal PC12 Cells*

p21c-Ha-Ras (Ras) can be activated by the guanine nucleotide exchange factor mSOS1 or byS-nitrosylation of cysteine 118 via nitric oxide (NO). To determine whether these two Ras-activating mechanisms modulate distinct biological effects, a NO-nonresponsive Ras mutant (RasC118S) was stably expressed in the PC12 cells, a cell line that generates NO upon nerve growth factor treatment. We report here that RasC118S functions indistinguishably from wild type Ras in activating and maintaining the mSOS1- and Raf-1-dependent mitogen-activated protein kinase cascade necessary for neuronal differentiation. However, continuous (>5 days) exposure to nerve growth factor reveals that, in contrast to parental or wild-type Ras-overexpressing PC12 cells, RasC118S-expressing PC12 cells cannot sustain the basal interaction between Ras and phosphatidylinositol 3-kinase. This results in spontaneous apoptosis of these cells despite the presence of nerve growth factor and serum. Thus unique downstream effector interactions and biological outcomes can be differentially modulated by distinct modes of Ras activation.
Impact of parasites on salmon recruitment in the Northeast Atlantic Ocean

Parasites may have large effects on host population dynamics, marine fisheries and conservation, but a clear elucidation of their impact is limited by a lack of ecosystem-scale experimental data. We conducted a meta-analysis of replicated manipulative field experiments concerning the influence of parasitism by crustaceans on the marine survival of Atlantic salmon (Salmo salar L.). The data include 24 trials in which tagged smolts (totalling 283 347 fish; 1996–2008) were released as paired control and parasiticide-treated groups into 10 areas of Ireland and Norway. All experimental fish were infection-free when released into freshwater, and a proportion of each group was recovered as adult recruits returning to coastal waters 1 or more years later. Treatment had a significant positive effect on survival to recruitment, with an overall effect size (odds ratio) of 1.29 that corresponds to an estimated loss of 39 per cent (95% CI: 18–55%) of adult salmon recruitment. The parasitic crustaceans were probably acquired during early marine migration in areas that host large aquaculture populations of domesticated salmon, which elevate local abundances of ectoparasitic copepods—particularly Lepeophtheirus salmonis. These results provide experimental evidence from a large marine ecosystem that parasites can have large impacts on fish recruitment, fisheries and conservation.