894 research outputs found
A cognitive analysis of event structure
Events occupy a central place in natural language. Accordingly, an understanding of them is crucial if one is to have any kind of a theoretically well-motivated account of natural language understanding and generation. It is proposed here that speakers create a cognitive structure for each discourse and process it as they introduce sentences into the discourse. The structure for each sentence depends systematically on its tense, aspect and the situation type; its effect on the discourse also depends on the structures of the sentences that precede it. It is also argued that the perfective aspect introduces the structure of the given event in its entirety. The progressive, by contrast, introduces only the core of the structure of the given event excluding, in particular, its preparatory processes and resultant state. Similarly, the perfect and the perfective can be distinguished on the basis of the temporal schemata they introduce. While the perfective presents the event as complete, the perfect presents it as complete and closed; i.e., the perfect prevents succeeding discourse from being interpreted as falling during the given event. This is surprising since the perfect is otherwise simply the combination of the perfective and a tense. This paper also provides a key motivation for distinguishing between the preparatory processes and the preliminary stages of an event. This observation, which is crucial in distinguishing between the perfective and the progressive has not been made in the literature
Interaction-based discovery of functionally important genes in cancers
A major challenge in cancer genomics is uncovering genes with an active role in tumorigenesis from a potentially large pool of mutated genes across patient samples. Here we focus on the interactions that proteins make with nucleic acids, small molecules, ions and peptides, and show that residues within proteins that are involved in these interactions are more frequently affected by mutations observed in large-scale cancer genomic data than are other residues. We leverage this observation to predict genes that play a functionally important role in cancers by introducing a computational pipeline (http://canbind.princeton.edu) for mapping large-scale cancer exome data across patients onto protein structures, and automatically extracting proteins with an enriched number of mutations affecting their nucleic acid, small molecule, ion or peptide binding sites. Using this computational approach, we show that many previously known genes implicated in cancers are enriched in mutations within the binding sites of their encoded proteins. By focusing on functionally relevant portions of proteinsāspecifically those known to be involved in molecular interactionsāour approach is particularly well suited to detect infrequent mutations that may nonetheless be important in cancer, and should aid in expanding our functional understanding of the genomic landscape of cancer
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Disentangling function from topology to infer the network properties of disease genes
Background: The topological features of disease genes within interaction networks are the subject of intense study, as they shed light on common mechanisms of pathology and are useful for uncovering additional disease genes. Computational analyses typically try to uncover whether disease genes exhibit distinct network features, as compared to all genes. Results: We demonstrate that the functional composition of disease gene sets is an important confounding factor in these types of analyses. We consider five disease sets and show that while they indeed have distinct topological features, they are also enriched in functions that a priori exhibit distinct network properties. To address this, we develop a computational framework to assess the network properties of disease genes based on a sampling algorithm that generates control gene sets that are functionally similar to the disease set. Using our function-constrained sampling approach, we demonstrate that for most of the topological properties studied, disease genes are more similar to sets of genes with similar functional make-up than they are to randomly selected genes; this suggests that these observed differences in topological properties reflect not only the distinguishing network features of disease genes but also their functional composition. Nevertheless, we also highlight many cases where disease genes have distinct topological properties even when accounting for function. Conclusions: Our approach is an important first step in extracting the residual topological differences in disease genes when accounting for function, and leads to new insights into the network properties of disease genes
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molBLOCKS: Decomposing small molecule sets and uncovering enriched fragments
The chemical structures of biomolecules, whether naturally occurring or synthetic, are composed of functionally important building blocks. Given a set of small moleculesāfor example, those known to bind a particular proteinācomputationally decomposing them into chemically meaningful fragments can help elucidate their functional properties, and may be useful for designing novel compounds with similar properties. Here we introduce molBLOCKS, a suite of programs for breaking down sets of small molecules into fragments according to a predefined set of chemical rules, clustering the resulting fragments, and uncovering statistically enriched fragments. Among other applications, our software should be a great aid in large-scale chemical analysis of ligands binding specific targets of interest
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Using context to improve protein domain identification
<p>Abstract</p> <p>Background</p> <p>Identifying domains in protein sequences is an important step in protein structural and functional annotation. Existing domain recognition methods typically evaluate each domain prediction independently of the rest. However, the majority of proteins are multidomain, and pairwise domain co-occurrences are highly specific and non-transitive.</p> <p>Results</p> <p>Here, we demonstrate how to exploit domain co-occurrence to boost weak domain predictions that appear in previously observed combinations, while penalizing higher confidence domains if such combinations have never been observed. Our framework, Domain Prediction Using Context (dPUC), incorporates pairwise "context" scores between domains, along with traditional domain scores and thresholds, and improves domain prediction across a variety of organisms from bacteria to protozoa and metazoa. Among the genomes we tested, dPUC is most successful at improving predictions for the poorly-annotated malaria parasite <it>Plasmodium falciparum</it>, for which over 38% of the genome is currently unannotated. Our approach enables high-confidence annotations in this organism and the identification of orthologs to many core machinery proteins conserved in all eukaryotes, including those involved in ribosomal assembly and other RNA processing events, which surprisingly had not been previously known.</p> <p>Conclusions</p> <p>Overall, our results demonstrate that this new context-based approach will provide significant improvements in domain and function prediction, especially for poorly understood genomes for which the need for additional annotations is greatest. Source code for the algorithm is available under a GPL open source license at <url>http://compbio.cs.princeton.edu/dpuc/</url>. Pre-computed results for our test organisms and a web server are also available at that location.</p
Study of knowledge, attitude, practices regarding PPIUCD among antenatal women at a tertiary care centre in Northern India
Background: PPIUCD has been introduced in the national family welfare program since March 2010 in several states. AN IUCD can be inserted in 48 hours postpartum, referred to here as postpartum intrauterine contraceptive device. This study was done to assess the Knowledge, attitude and practice of postpartum Intrauterine contraceptive device in antenatal patients at a tertiary care centre in Northern India.Methods: This is a questionnaire based cross sectional observational study including 350 antenatal women attending antenatal OPD over a period of 6 months.Results: Out of these 350 women, 126 women (36%) had knowledge of PPIUCD. only 30 % of women had previous knowledge about PPIUCD however only 10 % of women practiced it in the past. After appropriate counselling 18% of women agreed for insertion of PPIUCD after this delivery.Conclusions: The study concludes that the antenatal women had poor knowledge regarding PPIUCD. Practices were even worse. This might be attributed to low education ,Ā refusal by family especially male partner, and religious beliefs. But once appropriate knowledge and information is provided, attitude gradually changes
WASTE MANAGEMENT INITIATIVES IN INDIA FOR HUMAN WELL BEING
The objectives of writing this paper is to study the current practices related to the various waste management initiatives taken in India for human wellbeing. The other purpose is to provide some suggestions and recommendations to improve the waste management practices in Indian towns. This paper is based on secondary research. Existing reports related to waste management and recommendations of planners/NGOs/consultants/government accountability agencies/key industry experts/ for improving the system are studied. It offers deep knowledge about the various waste management initiatives in India and find out the scope for improvement in the management of waste for the welfare of the society. The paper attempts to understand the important role played by the formal sector engaged in waste management in our country. This work is original and could be further extended
Two critical positions in zinc finger domains are heavily mutated in three human cancer types
A major goal of cancer genomics is to identify somatic mutations that play a role in tumor initiation or progression. Somatic mutations within transcription factors are of particular interest, as gene expression dysregulation is widespread in cancers. The substantial gene expression variation evident across tumors suggests that numerous regulatory factors are likely to be involved and that somatic mutations within them may not occur at high frequencies across patient cohorts, thereby complicating efforts to uncover which ones are cancerrelevant. Here we analyze somatic mutations within the largest family of human transcription factors, namely those that bind DNA via Cys2His2 zinc finger domains. Specifically, to hone in on important mutations within these genes, we aggregated somatic mutations across all of them by their positions within Cys2His2 zinc finger domains. Remarkably, we found that for three classes of cancers profiled by The Cancer Genome Atlas (TCGA)ĆUterine Corpus Endometrial Carcinoma, Colon and Rectal Adenocarcinomas, and Skin Cutaneous Melanoma Ćtwo specific, functionally important positions within zinc finger domains are mutated significantly more often than expected by chance, with alterations in 18%, 10% and 43% of tumors, respectively. Numerous zinc finger genes are affected, with those containing KruĆppel- associated box (KRAB) repressor domains preferentially targeted by these mutations. Further, the genes with these mutations also have high overall missense mutation rates, are expressed at levels comparable to those of known cancer genes, and together have biological process annotations that are consistent with roles in cancers. Altogether, we introduce evidence broadly implicating mutations within a diverse set of zinc finger proteins as relevant for cancer, and propose that they contribute to the widespread transcriptional dysregulation observed in cancer cells
WASTE MANAGEMENT INITIATIVES IN INDIA FOR HUMAN WELL BEING
The objectives of writing this paper is to study the current practices related to the various waste management initiatives taken in India for human wellbeing. The other purpose is to provide some suggestions and recommendations to improve the waste management practices in Indian towns. This paper is based on secondary research. Existing reports related to waste management and recommendations of planners/NGOs/consultants/government accountability agencies/key industry experts/ for improving the system are studied. It offers deep knowledge about the various waste management initiatives in India and find out the scope for improvement in the management of waste for the welfare of the society. The paper attempts to understand the important role played by the formal sector engaged in waste management in our country. This work is original and could be further extended
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