Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Splicing Finder: an online bioinformatics tool to predict splicing signals

Thousands of mutations are identified yearly. Although many directly affect protein expression, an increasing proportion of mutations is now believed to influence mRNA splicing. They mostly affect existing splice sites, but synonymous, non-synonymous or nonsense mutations can also create or disrupt splice sites or auxiliary cis-splicing sequences. To facilitate the analysis of the different mutations, we designed Human Splicing Finder (HSF), a tool to predict the effects of mutations on splicing signals or to identify splicing motifs in any human sequence. It contains all available matrices for auxiliary sequence prediction as well as new ones for binding sites of the 9G8 and Tra2-β Serine-Arginine proteins and the hnRNP A1 ribonucleoprotein. We also developed new Position Weight Matrices to assess the strength of 5′ and 3′ splice sites and branch points. We evaluated HSF efficiency using a set of 83 intronic and 35 exonic mutations known to result in splicing defects. We showed that the mutation effect was correctly predicted in almost all cases. HSF could thus represent a valuable resource for research, diagnostic and therapeutic (e.g. therapeutic exon skipping) purposes as well as for global studies, such as the GEN2PHEN European Project or the Human Variome Project.
LEARNING WITHIN AND AMONG ORGANIZATIONS

This work was supported in part by the Office of Naval Research (ONR), United States Navy Grant No. N00014-97-1-0037 and by the National Science Foundation under Grant No. IRI9633 662. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the Office of Naval Research, the National Science Foundation, or the U.S. government.
Interactive components for visual exploration of multimedia archives

With the increase of online resources, one main challenge for multimedia content providers is to provide efficient and user friendly tools for a deep and shallow navigation adapted to large scale audiovisual content. This paper describes a generic framework to build visual interactive applications the objectives of which are to enhance the understanding and to allow easy access to multimedia resources and management. Visual Maps are built on multi-modal similarity matrices computed from automatically extracted descriptors and use graph clustering and layout methods. Active relevance feedback methods are applied to allow users to control the maps evolution according to their needs. The First results of users' evaluation are presented for one of our tools.
Snowball Earth: Asynchronous coupling of sea‐glacier flow with a global climate model

During Snowball Earth episodes of the Neoproterozoic and Paleoproterozoic, limited amounts of tropical open ocean (Jormungand), or tropical ocean with thin ice cover, would help to explain (1) vigorous glacial activity in low latitudes, (2) survival of photosynthetic life, and (3) deglacial recovery without excessive buildup of atmospheric CO2. Some previous models have suggested that tropical open ocean or thin‐ice cover is possible; however, its viability in the presence of kilometer‐thick sea glaciers flowing from higher latitudes has not been demonstrated conclusively. Here we describe a new method of asynchronously coupling a zonal sea‐glacier model with a 3‐D global climate model and apply it to Snowball Earth. Equilibrium curves of ice line versus CO2 are mapped out, as well as their dependence on ocean heat transport efficiency, sea‐glacier flow, and other model parameters. No climate states with limited tropical open ocean or thin ice are found in any of our model runs, including those with sea glaciers. If this result is correct, then other refugia such as cryoconite pans would have been required for life to survive. However, the reasons for the differences between our results and others should first be resolved. It is suggested that small‐scale convective dynamics, affecting fractional snow cover in low latitudes, may be a critical factor accounting for these differences.
Critical behavior of O(2)⊗O(N) symmetric models

We investigate the controversial issue of the existence of universality classes describing critical phenomena in three-dimensional statistical systems characterized by a matrix order parameter with symmetry O(2)xO(N) and symmetry-breaking pattern O(2)xO(N) -> O(2)xO(N-2). Physical realizations of these systems are, for example, frustrated spin models with noncollinear order. Starting from the field-theoretical Landau-Ginzburg-Wilson Hamiltonian, we consider the massless critical theory and the minimal-subtraction scheme without epsilon expansion. The three-dimensional analysis of the corresponding five-loop expansions shows the existence of a stable fixed point for N=2 and N=3, confirming recent field-theoretical results based on a six-loop expansion in the alternative zero-momentum renormalization scheme defined in the massive disordered phase. In addition, we report numerical Monte Carlo simulations of a class of three-dimensional O(2)xO(2)-symmetric lattice models. The results provide further support to the existence of the O(2)xO(2) universality class predicted by the field-theoretical analyses.
Development of the early axon scaffold in the rostral brain of the chick embryo

The arrangement of the early nerve connections in the embryonic vertebrate brain follows a well‐conserved pattern, forming the early axon scaffold. The early axon tracts have been described in a number of anamniote species and in mouse, but a detailed analysis in chick is lacking. We have used immunostaining, axon tracing and in situ hybridisation to analyse the development of the early axon scaffold in the embryonic chick brain in relation to the neuromeric organisation of the brain. The first tract to be formed is the medial longitudinal fascicle (MLF), shortly followed by the tract of the postoptic commissure to pioneer the ventral longitudinal tract system. The MLF was found to originate from three different populations of neurones located in the diencephalon. Neurones close to the dorsal midline of the mesencephalon establish the descending tract of the mesencephalic nucleus of the trigeminus. Their axons pioneer the lateral longitudinal tract. At later stages, the tract of the posterior commissure emerges in the caudal pretectum as the first transversal tract. It is formed by dorsally projecting axons from neurones located in the ventral pretectum, and by ventrally projecting axons from neurones located in the dorsal pretectum. The organisation of neurones and axons in the chick brain is similar to that described in the mouse, though tracts form in a different order and appear more clearly distinguished than in the mammalian model.
A new method for weighted fuzzy interpolative reasoning based on weights-learning techniques

This paper presents a weighted fuzzy interpolative reasoning method for sparse fuzzy rule-based systems which allows the antecedent variables appearing in the fuzzy rules to have different weights. We also present a weights-learning algorithm to automatically learn the optimal weights of the antecedent variables of the fuzzy rules for the proposed weighted fuzzy interpolative reasoning method. We apply the proposed weighted fuzzy interpolative reasoning method and the proposed weights-learning algorithm to deal with the truck backer-upper control problem. The experimental results show that the proposed fuzzy interpolative reasoning method using the optimally learned weights by the proposed weights-learning algorithm gets better truck backer-upper control results than the existing methods.
Epistasis within the MHC contributes to the genetic architecture of celiac disease

Epistasis has long been thought to contribute to the genetic aetiology of complex diseases, yet few robust epistatic interactions in humans have been detected. We have conducted exhaustive genome-wide scans for pairwise epistasis in five independent celiac disease (CD) case-control studies, using a rapid model-free approach to examine over 500 billion SNP pairs in total. We found 20 significant epistatic signals within the HLA region which achieved stringent replication criteria across multiple studies and were independent of known CD risk HLA haplotypes. The strongest independent CD epistatic signal corresponded to genes in the HLA class III region, in particular PRRC2A and GPANK1/C6orf47, which are known to contain variants for non-Hodgkin’s lymphoma and early menopause, co-morbidities of celiac disease. Replicable evidence for epistatic variants outside the MHC was not observed. Both within and between European populations, we observed striking consistency of epistatic models and epistatic model distribution. Within the UK population, models of CD based on both epistatic and additive single-SNP effects increased explained CD variance by approximately 1% over those of single SNPs. Models of only epistatic pairs or additive single-SNPs showed similar levels of CD variance explained, indicating the existence of a substantial overlap of additive and epistatic components. Our findings have implications for the determination of genetic architecture and, by extension, the use of human genetics for validation of therapeutic targets.
Advocating the Use of Imprecisely Observed Data in Genetic Fuzzy Systems

In our opinion, and in accordance with current literature, the precise contribution of genetic fuzzy systems to the corpus of the machine learning theory has not been clearly stated yet. In particular, we question the existence of a set of problems for which the use of fuzzy rules, in combination with genetic algorithms, produces more robust models, or classifiers that are inherently better than those arising from the Bayesian point of view. We will show that this set of problems actually exists, and comprises interval and fuzzy valued datasets, but it is not being exploited. Current genetic fuzzy classifiers deal with crisp classification problems, where the role of fuzzy sets is reduced to give a parametric definition of a set of discriminant functions, with a convenient linguistic interpretation. Provided that the customary use of fuzzy sets in statistics is vague data, we propose to test genetic fuzzy classifiers over imprecisely measured data and design experiments well suited to these problems. The same can be said about genetic fuzzy models: the use of a scalar fitness function assumes crisp data, where fuzzy models, a priori, do not have advantages over statistical regression.
Green Computing Knowledge among Students in a Ugandan University

Humans, including students, are partly responsible for rising levels of global warming through unsustainable computing practices. It is imperative that students participate in the global drive to reduce global warming through activities like green computing which advocates for sustainable use of computing resources to reduce energy consumption and carbon emissions. The study was conducted to establish green computing awareness levels of students from Islamic University in Uganda (IUIU) and also determine if such levels were influenced by computer experience. Results from a purposive sample of 452 students indicated that students' levels of green computing awareness were low, and computer experience influenced two of the three dimensions of perceived knowledge of green computing.
An Evaluation of the Usability of a Computerized Decision Support System for Nursing Homes

Summary Background: Computerized decision support systems (CDSSs) have the potential to significantly improve the quality of nursing care of older people by enhancing the decision making of nursing personnel. Despite this potential, health care organizations have been slow to incorporate CDSSs into nursing home practices. Objective: This study describes facilitators and barriers that impact the ability of nursing personnel to effectively use a clinical CDSS for planning and treating pressure ulcers (PUs) and malnutrition and for following the suggested risk assessment guidelines for the care of nursing home residents. Methods: We employed a qualitative descriptive design using varied methods, including structured group interviews, cognitive walkthrough observations and a graphical user interface (GUI) usability evaluation. Group interviews were conducted with 25 nursing personnel from four nursing homes in southern Norway. Five nursing personnel participated in cognitive walkthrough observations and the GUI usability evaluation. Text transcripts were analyzed using qualitative content analysis. Results: Group interview participants reported that ease of use, usefulness and a supportive work environment were key facilitators of CDSS use. The barriers identified were lack of training, resistance to using computers and limited integration of the CDSS with the facility’s electronic health record (EHR) system. Key findings from the usability evaluation also identified the difficulty of using the CDSS within the EHR and the poorly designed GUI integration as barriers. Conclusion: Overall, we found disconnect between two types of nursing personnel. Those who were comfortable with computer technology reported positive feedback about the CDSS, while others expressed resistance to using the CDSS for various reasons. This study revealed that organizations must invest more resources in educating nursing personnel on the seriousness of PUs and poor nutrition in the elderly, providing specialized CDSS training and ensuring that nursing personnel have time in the workday to use the CDSS.
Learnt Quasi-Transitive Similarity for Retrieval from Large Collections of Faces

We are interested in identity-based retrieval of face sets from large unlabelled collections acquired in uncontrolled environments. Given a baseline algorithm for measuring the similarity of two face sets, the meta-algorithm introduced in this paper seeks to leverage the structure of the data corpus to make the best use of the available baseline. In particular, we show how partial transitivity of inter-personal similarity can be exploited to improve the retrieval of particularly challenging sets which poorly match the query under the baseline measure. We: (i) describe the use of proxy sets as a means of computing the similarity between two sets, (ii) introduce transitivity meta-features based on the similarity of salient modes of appearance variation between sets, (iii) show how quasi-transitivity can be learnt from such features without any labelling or manual intervention, and (iv) demonstrate the effectiveness of the proposed methodology through experiments on the notoriously challenging YouTube database.
Cd-Specific Mutants of Mercury-Sensing Regulatory Protein MerR, Generated by Directed Evolution

ABSTRACT The mercury-sensing regulatory protein, MerR (Tn21), which regulates mercury resistance operons in Gram-negative bacteria, was subjected to directed evolution in an effort to generate a MerR mutant that responds to Cd but not Hg. Oligonucleotide-directed mutagenesis was used to introduce random mutations into the key metal-binding regions of MerR. The effects of these mutations were assessed using a vector in which MerR controlled the expression of green fluorescent protein (GFP) and luciferase via the mer operator/promoter. An Escherichia coli cell library was screened by fluorescence-activated cell sorting, using a fluorescence-based dual screening strategy that selected for MerR mutants that showed GFP repression when cells were induced with Hg but GFP activation in the presence of Cd. Two Cd-responsive MerR mutants with decreased responses toward Hg were identified through the first mutagenesis/selection round. These mutants were used for a second mutagenesis/selection round, which yielded eight Cd-specific mutants that had no significant response to Hg, Zn, or the other tested metal(loid)s. Seven of the eight Cd-specific MerR mutants showed repressor activities equal to that of wild-type (wt) MerR. These Cd-specific mutants harbored multiple mutations (12 to 22) in MerR, indicating that the alteration of metal specificity with maintenance of repressor function was due to the combined effect of many mutations rather than just a few amino acid changes. The amino acid changes were studied by alignment against the sequences of MerR and other metal-responsive MerR family proteins. The analysis indicated that the generated Cd-specific MerR mutants appear to be unique among the MerR family members characterized to date.
Capacity dynamics and endogenous asymmetries in firm size

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Processing of a Composite Large Subunit rRNA: Studies with Chlamydomonas Mutants Deficient in Maturation of the 23S-like rRNA

Maturation of the chloroplast 23S-like rRNA involves the removal of internal transcribed spacers (ITSs) and, in the case of Chlamydomonas reinhardtii, the splicing of a group I intron (Cr.LSU). Little is known of the cis and trans requirements or of the processing pathway for this essential RNA. Previous work showed that the ribosome-deficient ac20 mutant overaccumulates an unspliced large subunit (LSU) RNA, suggesting that it might be a splicing mutant. To elucidate the molecular basis of the ac20 phenotype, a detailed analysis of the rrn transcripts in ac20 and wild-type cells was performed. The results indicate that processing of the ITSs, particularly ITS-1, is inefficient in ac20 and that ITS processing occurs after splicing. Deletion of the Cr.LSU intron from ac20 also did not alleviate the mutant phenotype. Thus, the primary defect in ac20 is not splicing but most likely is associated with ITS processing. A splicing deficiency was studied by transforming wild-type cells with rrnL genes containing point mutations in the intron core. Heteroplasmic transformants were obtained in most cases, except for P4 helix mutants; these strains grew slowly, were light sensitive, and had an RNA profile indicative of inefficient splicing. Transcript analysis in the P4 mutants also indicated that ITS processing can occur on an unspliced precursor, although with reduced efficiency. These latter results indicate that although there is not an absolutely required order for LSU processing, there does seem to be a preferred order that results in efficient processing in vivo.
Prediction of adjuvant chemotherapy response in triple negative breast cancer with discovery and targeted proteomics

Background Triple-negative breast cancer (TNBC) accounts for 15–20% of all breast cancers and usually requires the administration of adjuvant chemotherapy after surgery but even with this treatment many patients still suffer from a relapse. The main objective of this study was to identify proteomics-based biomarkers that predict the response to standard adjuvant chemotherapy, so that patients at are not going to benefit from it can be offered therapeutic alternatives. Methods We analyzed the proteome of a retrospective series of formalin-fixed, paraffin-embedded TNBC tissue applying high-throughput label-free quantitative proteomics. We identified several protein signatures with predictive value, which were validated with quantitative targeted proteomics in an independent cohort of patients and further evaluated in publicly available transcriptomics data. Results Using univariate Cox analysis, a panel of 18 proteins was significantly associated with distant metastasis-free survival of patients (p<0.01). A reduced 5-protein profile with prognostic value was identified and its prediction performance was assessed in an independent targeted proteomics experiment and a publicly available transcriptomics dataset. Predictor P5 including peptides from proteins RAC2, RAB6A, BIEA and IPYR was the best performance protein combination in predicting relapse after adjuvant chemotherapy in TNBC patients. Conclusions This study identified a protein combination signature that complements histopathological prognostic factors in TNBC treated with adjuvant chemotherapy. The protein signature can be used in paraffin-embedded samples, and after a prospective validation in independent series, it could be used as predictive clinical test in order to recommend participation in clinical trials or a more exhaustive follow-up.
Impact of global genome repair versus transcription-coupled repair on ultraviolet carcinogenesis in hairless mice.

The nucleotide excision repair (NER) system is comprised of two subpathways, i.e., transcription-coupled repair (TCR) and global genome repair (GGR). To establish the relative importance of TCR and GGR for UV effects on the skin, we have used hairless knockout mouse strain lacking either TCR (CSB -/-) or GGR (XPC -/-). In single exposure experiments, we found that CSB -/- mice have a 7-16 times higher susceptibility to sunburn than XPC -/- mice and than heterozygous (+/-) and wild-type (+/+) controls. Exposure to 80 J/m2 UV radiation (i.e., suberythemogenic in CSB -/-) on 10 consecutive days gives rise to epidermal hyperplasia in CSB -/- and XPC -/-, whereas repair-proficient controls do not show epidermal hyperplasia from these exposures. In addition, CSB -/- mice develop marked parakeratosis, whereas XPC -/- mice and controls do not. Under continued exposure to this daily dose, squamous cell carcinomas appear in CSB -/-, XPC -/-, and in the control groups, whereas only in the CSB -/- animals is a fairly high number of benign papillomas also found. The median latency time of squamous cell carcinomas (diameters > or = 1 mm) is 84 days for the XPC -/- mice, 115 days for the CSB -/- mice, and 234-238 days for the heterozygous and wild-type control groups. These results indicate that GGR is more important than TCR in protection against UV-induced carcinomas of the skin but not against other UV effects such as sunburn, epidermal thickening, scaling of the stratum corneum, and development of papillomas. These results also indicate that GGR capacity may serve as a better predictor for skin cancer susceptibility than sensitivity to sunburn. The relative cancer susceptibilities of GGR- and TCR-deficient skin could well depend on the balance between an increased mutation rate and the presence (in CSB -/-) or lack (in XPC -/-) of a compensatory apoptotic response.