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Essay on The Life and Experiences of Winston Churchill

I chose Winston Churchill a political leader (Nov. 30, 1874-Jan. 24, 1965). In Winston Churchill’s early years as a child his parents were always traveling and had very busy social lives. Mrs. Everest was his nanny that took good care of him. At age eight he attended boarding school where he was considered as a troublemaker. At age twelve he was accepted in Military School where he studied military tactics. Later he graduated and worked for the Morning Post during the Boer War in South Africa. He had quite an adventure during this time, he was shot at and captured but managed to escape where he lived to write a book about it. During fighting the war Winston Churchill knew that he wanted to get into politics to make policies to make a†¦show more content†¦Sir Felix Semen gave him speech exercises such as â€Å"The Spanish ships I cannot see for they are not in sight† he would constantly practice. Later on he was told by American masseuse that his tongue was res trained by a ligament that no one else has, which caused all of his stuttering and rattling of the throat problems. He wanted the ligament to be removed but Sir Felix Semen refused. Winston Churchill learned to live with this and before every speech he would practice the speech over and over to make sure that his stuttering was under control. He kept saying that he was going to be a political speaker; eventually he gave a well-spoken political speech which he said â€Å"My impediment is no hindrance† (Rosenberg, J. 2014). I thought by Winston Churchill making this speech was amazing because he was letting the world know that nothing is going to set him back. Winston Churchill acted out of social interest because ever since he was a young boy he knew that he wanted to go to school to learn about the war and to become a political leader. 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Literature-based discovery of diabetes Free Essays

string(140) " in the form of HGNC \[HUGO \(Human Genome Organization\) Gene Nomenclature Committee\] genes, were confirmed by manual review of the text\." Reactive oxygen species (ROS) are known mediators of cellular damage in multiple diseases including diabetic complications. Despite its importance, no comprehensive database is currently available for the genes associated with ROS. Methods We present ROS- and diabetes-related targets (genes/proteins) collected from the biomedical literature through a text mining technology. We will write a custom essay sample on Literature-based discovery of diabetes or any similar topic only for you Order Now A web-based literature mining tool, SciMiner, was applied to 54 biomedical papers indexed with diabetes and ROS by PubMed to identify relevant targets. Over-represented targets in the ROS-diabetes literature were obtained through comparisons against randomly selected literature. The expression levels of nine genes, selected from the top ranked ROS-diabetes set, were measured in the dorsal root ganglia (DRG) of diabetic and non-diabetic DBA/2J mice in order to evaluate the biological relevance of literature- derived targets in the pathogenesis of diabetic neuropathy. Results SciMiner identified 1,026 ROS- and diabetes-related targets from the 54 biomedical papers (http://Jdrf. eurology. med. umich. edu/ROSDiabetes/ webcite). Fifty-three targets were significantly over-represented in the ROS-diabetes literature ompared to randomly selected literature. These over-represented targets included well-known members of the oxidative stress response including catalase, the NADPH oxidase family, and the superoxide dismutase family of proteins. Eight of the nine selected genes exhibited significant differential expression between diabetic and n on-diabetic mice. For six genes, the direction of expression change in diabetes paralleled enhanced oxidative stress in the DRG. Conclusions Literature mining compiled ROS-diabetes related targets from the biomedical literature and led us to evaluate the biological relevance of selected targets in the athogenesis of diabetic neuropathy. Diabetes is a metabolic disease in which the body does not produce or properly respond to insulin, a hormone required to convert carbohydrates into energy for daily life. According to the American Diabetes Association, 23. million children and adults, approximately 7. 8% of the population in the United States, have diabetes [1]. The cost of diabetes in 2007 was estimated to be $174 billion [1]. The micro- and macro-vascular complications of diabetes are the most common causes of renal tailure, blindness and amputations leading to significant morta y, morbidity poor quality of life; however, incomplete understanding of the causes of diabetic complications hinders the de velopment of mechanism-based therapies. In vivo and in vitro experiments implicate a number of enzymatic and non-enzymatic metabolic pathways in the initiation and progression of diabetic complications [2] including: (1) increased polyol pathway activity leading to sorbitol and fructose accumulation, NAD(P)-redox imbalances and changes in signal transduction; (2) non- enzymatic glycation of proteins yielding â€Å"advanced glycation end-products† (AGES); (3) ctivation of protein kinase C (PKC), initiating a cascade of intracellular stress responses; and (4) increased hexosamine pathway flux [2,3]. Only recently has a link among these pathways been established that provides a unified mechanism of tissue damage. Each of these pathways directly and indirectly leads to overproduction of reactive oxygen species (ROS) [23]. ROS are highly reactive ions or small molecules including oxygen ions, free radicals and peroxides, formed as natural byproducts of cellular energy metabolism. ROS are implicated in multiple cellular pathways such as mitogen-activated protein kinase MAPK) signaling, c-Jun amino-terminal kinase ONK), cell proliferation and apoptosis [4-6]. Due to the highly reactive properties of ROS, excessive ROS may cause significant damage to proteins, DNA, RNA and lipids. All cells express enzymes capable of neutralizing ROS. In addition to the maintenance of antioxidant systems such as glutathione and thioredoxins, primary sensory neurons express two main detoxifying enzymes: superoxide dismutase (SOD) [7] and catalase [8]. SOD converts superoxide (02-) to H202, which is reduced to H20 by glutathione and catalase [8]. SODI is the main form of SOD in the cytoplasm; SOD2 is located within the itochondria. In neurons, SODI activity represents approximately 90% of total SOD activity and SOD2 approximately 10% [9]. Under diabetic conditions, this protective mechanism is overwhelmed due to the substantial increase in ROS, leading to cellular damage and dysfunction [10]. The idea that increased ROS and oxidative stress contribute to the pathogenesis of diabetic complications has led scientists to investigate different oxidative stress pathways [7,11]. Inhibition of ROS or maintenance of euglycemia restores metabolic and vascular imbalances and blocks both the initiation and progression of omplications [1 2,13]. Despite the significant implications and extensive research into the role of ROS in diabetes, no comprehensive database regarding ROS-related genes or proteins is currently available. In the present study, a comprehensive list of ROS- and diabetes-related targets (genes/proteins) was compiled from the biomedical literature through text mining technology. SciMiner, a web-based literature mining tool [14], was used to retrieve and process documents and identify targets from the text. SciMiner provides a convenient web-based platform for target-identification within the biomedical iterature, similar to other tools including EBIMed [1 5], ALI BABA [16], and Polysearch [1 7]; however, SciMiner is unique in that it searches tull text documents, suppo free-text PubMed query style, and allows the comparison of target lists from multiple queries. The ROS-diabetes targets collected by SciMiner were further tested against randomly selected non-ROS-diabetes literature to identify targets that are significantly over- represented in the ROS-diabetes literature. Functional enrichment analyses were performed on these targets to identify significantly over-represented biological unctions in terms of Gene Ontology (GO) terms and pathways. In order to confirm the biological relevance of the over-represented ROS-diabetes targets, the gene expression levels of nine selected targets were measured in dorsal root ganglia (DRG) from mice with and without diabetes. DRG contain primary sensory neurons that relay information from the periphery to the central nervous system (CNS) Unlike the CNS, DRG are not protected by a blood-nerve barrier, and are consequently vulnerable to metabolic and toxic injury [19]. We hypothesize that differential expression of identified targets in DRG would confirm heir involvement in the pathogenesis of diabetic neuropathy. Defining ROS-diabetes literature To retrieve the list of biomedical literature associated with ROS and diabetes, PubMed was queried using (â€Å"Reactive Oxygen Species†[MeSH] AND â€Å"Diabetes Mellitus†[MeSH]). This query yielded 54 articles as of April 27, 2009. SciMiner, a web-based literature mining tool [14], was used to retrieve and process the abstracts and available full text documents to identify targets (full text documents were available for approximately 40% of the 1 , 1 54 articles). SciMiner-identified targets, eported in the form of HGNC [HUGO (Human Genome Organization) Gene Nomenclature Committee] genes, were confirmed by manual review of the text. You read "Literature-based discovery of diabetes" in category "Papers" Comparison with human curated data (NCBI Gene2PubMed) The NCBI Gene database provides links between Gene and PubMed. The links are the result of (1) manual curation within the NCBI via literature analysis as part of generating a Gene record, (2) integration of information from other public databases, and (3) GeneRlF (Gene Reference Into Function) in which human experts provide a brief summary of gene functions and make the connections between citation PubMed) and Gene databases. For the 54 ROS-diabetes articles, gene-paper associations were retrieved from the NCBI Gene database. Non-human genes were mapped to homologous human genes through the NCBI HomoloGene database. The retrieved genes were compared against the SciMiner derived targets. Any genes missed by SciMiner were added to the ROS-diabetes target set. Protein-protein interactions among ROS-diabetes targets To indirectly examine the association of literature derived targets (by SciMiner and NCBI Gene2PubMed) with ROS and diabetes, protein-protein interactions (PPIs) mong the targets were surveyed This was based on an assumption that targets are more likely to have PPIs with each other if they are truly associated within the same biological functions/pathways. A PPI network of the ROS-diabetes targets was generated using the Michigan Molecular Interactions (MIMI, http://mimi. ncibi. org/ webcite) database [20] and compared against 100 PPI networks of randomly drawn sets (the same number of the ROS-diabetes target set) from HUGO. A standard Z-test and one sample T-test were used to calculate the statistical significance of the ROS- diabetes PPI network with respect to the random PPI networks. Functional enrichment analysis Literature derived ROS-diabetes targets (by SciMiner and NCBI Gene2PubMed) were subject to functional enrichment analyses to identify significantly over-represented biological functions in terms of Gene Ontology [21], pathways (Kyoto Encyclopedia of Genes and Genomes (KEGG, http://www. genome. ]p/kegg/ webcite) [22] and Reactome http://www. reactome. org/ webcite[23]). Fisher’s exact test [24] was used to calculate the statistical significance of these biological functions with BenJamini-Hochberg (BH) adjusted p-value ; 0. 5 [25] as the cut-off. Over-represented ROS-diabetes targets Defining background corpora To identify a subset of targets that are highly over-represented within the ROS- diabetes targets, the frequency of each target (defined as the number of documents in which the target was identified divided by the number of total documents in the query) was compared against the frequencies in randomly selected background corpora. Depending on how the background set is defined, over-represented targets may vary widely; therefore, to maintain the background corpora close to the ROS and diabetes context, documents were selected from the same Journal, volume, and issue f the 54 ROS-diabetes documents, but were NOT indexed with â€Å"Reactive Oxygen Species†[MeSH] nor â€Å"Diabetes Mellitus†[MeSH]. For example, one of the ROS-diabetes articles (PMID: 18227068), was published in the Journal of Biological Chemistry, Volume 283, Issue 16. This issue contained 85 papers, 78 of which were not indexed with either â€Å"Reactive Oxygen Species†[MeSH] or â€Å"Diabetes Mellitus†[MeSH] indexed. One of these 78 papers was randomly selected as a background document. Three sets of 54 documents were selected using this approach and processed using SciMiner. Identified targets were confirmed by manual review for accuracy. Identifying significantly over-represented targets ROS-diabetes targets were tested for over-representation against targets identified from the three background sets. Fisher’s exact test was used to determine if the frequency of each target in the ROS-diabetes target set was significantly different from that of the background sets. Any targets with a BH adjusted p-value 0. 5 in at least two of the three comparisons were deemed to be an over-represented ROS- diabetes target. Functional enrichment analyses were performed on these over- represented ROS-diabetes targets as described above. Selecting targets tor real-time R A subset of targets were selected for RT-PCR from the top 10 over-represented ROS- diabetes targets excluding insulin and NADPH oxidase 5 (NOX5), which does not have a mouse ortholog. Nitric oxide synthase 1 (NOSI), the main generator of nitric oxide, ranked at the 1 5th position and was additionally selected for inclusion in the test set. Differential gene expression by real-time RT-PCR Mice DBA/2J mice were purchased from the Jackson Laboratory (Bar Harbor, ME). Mice were housed in a pathogen-free environment and cared for following the University of Michigan Committee on the Care and Use of Animals guidelines. Mice were fed AIN76A chow (Research Diets, New Brunswick, NJ). Male mice were used for this study. Induction of diabetes Two treatment groups were defined: control (n = 4) and diabetic (n = 4). Diabetes was induced at 13 weeks of age by low-dose streptozotocin (STZ) injections, 50 mg/kg/day for five consecutive days. All diabetic mice received LinBit sustained release insulin implants (LinShin, Toronto, Canada) at 8 weeks post-STZ treatment. Insulin implants were replaced every 4 weeks, at 12 and 16 weeks post-STZ treatment. At 20 weeks post-STZ treatment, mice were euthanized by sodium pentobarbital overdose and DRG were harvested as previously described [26]. Real-time RT-PCR The gene expression of the selected nine literature-derived ROS-diabetes targets in DRG was measured using real-time RT-PCR in duplicate. The amount of mRNA isolated from each DRG was normalized to an endogenous reference [Tbp: TATA box binding protein; A cycle threshold (CT)]. Identification of ROS-diabetes targets A total of 1,021 unique targets were identified by SciMiner from the 1,154 ROS- diabetes papers defined by the query of (â€Å"Reactive Oxygen Species†[MeSH] AND â€Å"Diabetes Mellitus†[MeSH]) and confirmed by manual review. Table 1 contains the op 10 most frequently mentioned targets in the ROS-diabetes papers. Insulin was the most frequently mentioned target, followed by superoxide dismutase 1 and catalase. Table 1 . Top 10 most frequent ROS-diabetes targets The NCBI Gene2PubMed database, containing expert-curated associations between the NCBI Gene and PubMed databases, revealed 90 unique genes associated with the 54 ROS-diabetes papers (Additional File 1). SciMiner identified 85 out of these 90 targets, indicating a 94% recall rate. Five targets missed by SciMiner were added to the initial ROS-diabetes target set to result in 1,026 unique targets (Additional File 2). Additional tile 1. The list ot 90 genes trom the NCBI Gene2PubMed database tor the ROS-Diabetes literature (1 , 1 54 papers). Format: XLS Size: 35KB Download file This file can be viewed with: Microsoft Excel Vieweropen Data Additional file 2. The list of 1,026 ROS-Diabetes targets. Format: XLS Size: 229KB Download file This file can be viewed with: Microsoft Excel Vieweropen Data PPI network of the ROS-diabetes targets The PPI network among the ROS-diabetes targets was evaluated using MIMI interaction data. This was based on the assumption that targets commonly related to certain topic are more likely to have frequent interactions with each other. One hundred PPI networks were generated for comparison using the same number of genes (1,026) randomly selected from the complete HUGO gene set (25,254). The PPI network of the ROS-diabetes targets was significantly different from the randomly generated networks indicating their strong association with the topic â€Å"ROS and Diabetes†. Table 2 demonstrates that the mean number of targets with any PPI interaction in the randomly generated target sets was 528. 9 (approximately 52% of 1,026 targets), while the number of targets with any PPI interaction in the ROS- iabetes target was 983 (96%). The number of targets interacting with each other was also significantly different between the random networks (mean = 155. 4) and the ROS-diabetes network (mean = 879). Figure 1 illustrates the distributions of these measurements from the 100 random networks with the ROS-diabetes set depicted as a red vertical line. It is obvious that the PPI network of the ROS-diabetes targets is significantly different from the random networks. Table 2. Summary of 100 randomly generated PPI networks thumbnailFigure 1 . Histograms of randomly generated PPI networks. The histograms llustrate the distributions of 100 randomly generated networks, while the red line indicates the ROS-diabetes targets. The network of the ROS-diabetes targets is significantly different from the 100 randomly generated networks, indicating the overlap of ROS-diabetes targets with respect to the topic â€Å"Reactive Oxygen Species and Diabetes†. Functional enrichment analyses of the ROS-diabetes targets Functional enrichment analyses of the 1,026 ROS-diabetes targets were performed to identify over-represented biological functions of the ROS-diabetes targets. After BenJamini-Hochberg correction, a total of 189 molecular functions, 450 biological rocesses, 73 cellular components and 341 pathways were significantly enriched in the ROS-diabetes targets when compared against all the HUGO genes (see Additional Files 3, 4, 5 and 6 for the full lists). Table 3 lists the top 3 most over-represented GO terms and pathways ranked by p-values of Fisher’s exact test: e. g. , apoptosis, oxidoreductase activity and insulin signaling pathway. Additional file 3. The enriched Molecular Functions Gene Ontology Terms in the 1,026 ROS-Diabetes targets. Format: XLS Size: 91 KB Download file This file can be viewed with: Microsoft Excel Vieweropen Data Additional file 4. The nriched Biological Processes Gene Ontology Terms in the 1,026 ROS-Diabetes targets. Format: XLS Size: 95KB Download file This tile can be viewed wit Microsott Excel Vieweropen Data Additional tile enriched Cellular Components Gene Ontology Terms in the 1,026 ROS-Diabetes targets. Format: XLS Size: 61 KB Download file This file can be viewed with: Microsoft Excel Vieweropen Data Additional file 6. The enriched pathways in the 1,026 ROS-Diabetes targets. Format: XLS Size: 104KB Download file This file can be viewed with: Microsoft Excel Vieweropen Data Table 3. Enriched functions of 1,026 ROS-diabetes targets Identification of over-represented ROS-diabetes targets To identify the ROS-diabetes targets highly over-represented in ROS-diabetes literature, three sets of background corpora of the same size (n = 1 , 1 54 documents) were generated using the same Journal, volume and issue approach. The overlap among the three background sets in terms of documents and identified targets are illustrated in Figure 2. Approximately 90% of the selected background documents were unique to the individual set, while 50% of the identified targets were identified in at least one of the three background document sets. The frequencies of the identified targets were compared among the background sets for significant differences. None of the targets had a BH adjusted p-value ; 0. 05, indicating no significant difference among the targets from the three different background sets (See Additional File 7). thumbnailFigure 2. Venn diagrams of document compositions and identified targets of the randomly generated background sets. Approximately 90% of the selected background documents were unique to individual set (A), while 50% of the identified targets were identified in at least one of the three background document sets (B). Additional file 7. Comparisons of target frequencies among three background sets. Format: XLS Size: 22KB Download file This file can be viewed with: Microsoft Excel Vieweropen Data Comparisons of the ROS-diabetes targets against these background sets revealed 53 highly over- represented ROS-diabetes targets as listed in Table 4. These 53 targets were significant (p-value ; 0. 05) against all three background sets and significant following BenJamini-Hochberg multiple testing correction (BH adjusted p-value ; 0. 05) against at least two of the three background sets. SODI was the most over-represented in he ROS-diabetes targets. Table 4. 53 targets over-represented in ROS-diabetes literature Functional enrichment analyses of the over-represented ROS-diabetes targets Functional enrichment analyses of the 53 ROS-diabetes targets were performed to identify over- represented biological functions. Following BenJamini-Hochberg correction, a total of 65 molecular functions, 209 biological processes, 26 cellular components and 108 pathways were significantly over-represented when compared against all the HUGO genes (see Additional Files 8, 9, 10 and 11 for the full lists). Table 5 shows the top 3 ost significantly over-represented GO terms and pathways ranked by p-values of Fisher’s exact test. GO terms related to oxidative stress such as â€Å"superoxide metabolic process†, â€Å"superoxide release†, â€Å"electron carrier activity† and â€Å"mitochondrion† were highly over-represented 53 ROS-diabetes targets Additional file 8. The enriched Molecular Functions Gene Ontology Terms in the Over- represented 53 ROS-Diabetes targets. Format: XLS Size: 46KB Download file This file can be viewed with: Microsoft Excel Vieweropen Data Additional file 9. The enriched Biological Processes Gene Ontology Terms in the Over-represented 53 ROS- Diabetes targets. Format: XLS Size: 95KB Download file This file can be viewed with: Microsoft Excel Vieweropen Data Additional file 10. The enriched Cellular Components Gene Ontology Terms in the Over-represented 53 ROS-Diabetes targets. Format: XLS Size: 66KB Download file This file can be viewed with: Microsoft Excel Vieweropen Data Additional file 1 1 . The enriched pathways in the Over-represented 53 ROS-Diabetes targets. Format: XLS Size: 75KB Download file This file can be viewed with: Microsoft Excel Vieweropen Data Table 5. Enriched functions of the 53 over-represented targets in diabetes Gene expression change in iabetes Two groups of DBA/2J mice exhibited significantly different levels of glycosylated hemoglobin (%GHb). The mean ? ± SEM were 6. 2 ? ± 0. for the non-diabetic control group and for 14. 0 ? ± 0. 8 for the diabetic group (p-value 0. 001), indicative of prolonged hyperglycemia in the diabetic group [26]. DRG were harvested from these animals for gene expression assays. Nine genes were selected from the top ranked ROS-diabetes targets: superoxide dismutase 1 (Sodl), catalase (Cat), xanthine dehydrogenase (Xdh), protein kinase C alpha (Prkca), neutrophil cytosolic factor 1 Ncfl), nitric oxid e synthase 3 (Nos3), superoxide dismutase 2 (Sod2), cytochrome b-245 alpha (Cyba), and nitric oxide synthase 1 (Nosl). Eight genes exhibited differential expression between diabetic and non-diabetic mice (p-value 0. 05) as shown in Figure 3. Cat, Sodl, Sod2, Prkca, and NOSI expression levels were decreased, while Ncfl , Xdh, and Cyba expression levels were increased in diabetes. thumbnailFigure 3. Gene expression levels of selected ROS-diabetes targets in DRG examined by real-time RT-PCR. Expression levels are relative to Tbp, an internal control (error bar = SEM) (*, p 0. 05; **, p 0. 01; ***, p 0. 01). Eight (Cat, Sodl, Ncfl , Xdh, Sod2, Cyba, Prkca, and Nosl) out of the nine selected ROS-diabetes genes were significantly regulated by diabetes. Discussion Reactive oxygen species (ROS) are products of normal energy metabolism and play important roles in many other biological processes such as the immune response and signaling cascades [4-6]. As mediators of cellular damage, ROS are implicated in pathogenesis of multiple diseases including diabetic complications [27-30]. With the aid of literature mining technology, we collected 1 ,026 possible ROS-related targets from a set of biomedical literature indexed with both ROS and diabetes. Fifty-three targets were significantly over-represented in the ROS-diabetes papers when compared against three background sets. Depending on how the background set is defined, the over-represented targets may vary widely. An ideal background set would be the entire PubMed set; however, this is not possible due to limited access to tull texts and intense data processing. An alternative method wou d be to use only abstracts in PubMed, but this may not fully represent the literature. Using only the abstracts, our target identification method resulted in 21 (39%) of the 53 key ROS- iabetes targets (Additional File 12), suggesting the benefit of rich information in full text documents. In the present study, background documents were randomly selected from the same Journal, volume, and issue of the 54 ROS-diabetes documents, which were not indexed with â€Å"Reactive Oxygen Species†[MeSH] nor â€Å"Diabetes Mellitus†[MeSH]. This approach maintained the background corpora not far from the ROS and diabetes context. Additional file 12. The Key 53 ROS-Diabetes Targets Identifiable Using Only the Abstracts. Format: XLS Size: 23KB Download file This file can be viewed with: Microsoft Excel Vieweropen Data The gene expression evels of nine targets selected from the 53 over-represented ROS-diabetes targets were measured in diabetic and non-diabetic DRG. Our laboratory is particularly interested in deciphering the underlying mechanisms of diabetic neuropathy, a major complication of diabetes. Data published by our laboratory both in vitro and in vivo confirm the negative impact of oxidative stress in complication-prone neuron tissues like DRG In an effort to obtain diabetic neuropathy specific targets, SciMiner was employed to further analyze a subset of the ROS-diabetes papers (data not shown). Nerve growth factor (NGF) was identified as the most over- epresented target in this subset when compared to the full ROS-diabetes set; however, NGF did not have statistical significance (BH adjusted p-value = 0. 06). The relatively small numbers of papers and associated targets may have contributed to this non-significance. Therefore, the candidate targets for gene expression validation were selected from among the 53 over-represented ROS-diabetes targets derived from the full ROS-diabetes corpus. Among the tested genes, the expression levels of Cat, Sodl , Sod2, Prkca, and NOSI were decreased, while the expression levels of Ncfl , Xdh, and Cyba were increased nder diabetic conditions. Cat, Sodl , and Sod2 are responsible for protecting cells from oxidative stress by destroying superoxides and hydrogen peroxides [8-11]. Decreased expression of these genes may result in oxidative stress [32]. Increased expression of Cyba and Ncfl , subunits of superoxide-generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex [30], also supports enhanced oxidative stress. Xdh and its inter-convertible form, Xanthine oxidase (Xod), showed increased activity in various rat tissues under oxidative stress conditions ith diabetes [33], and also showed increased expression in diabetic DRG in the current study. Unlike the above concordant genes, protein kinase C and nitric oxide synthases did not exhibit predicted expression changes in diabetes. Protein kinase C activates NADPH oxidase, further promoting oxidative stress in the cell [34,35]. Decreased expression of Prkca in our diabetic DRG is not parallel with expression levels of other enzymes expected to increase oxidative stress. Between the two nitric oxide synthases tested in the present study, NOSI (neuronal) expression was significantly decreased (p-value 0. 01) in diabetes, while Nos3 (endothelial) expression was not significant (p-value = 0. 06). The neuronal NOSI is expected to play a major role in producing nitric oxide, another type of highly reactive free radical. Thus, with some exceptions, the majority of the differentially expressed genes in DRG show parallel results to the known activities of these targets in diabetes, suggesting enhanced oxidative stress in the diabetic DRG. Assessment of antioxidant enzyme expression in diabetes has yielded a variety of results [36-40] depending upon the duration of diabetes, the tissue studied and other factors. In diabetic mice and rats, it is commonly reported that superoxide dismutases are down-regulated [37-40], where data regarding catalase are variable [36,40]. PKC is activated in diabetes, but most papers that examined mRNA demonstrated that its expression is largely unchanged [41]. Among the 53 over-represented ROS-diabetes targets, SODI was the most over- represented and was differentially expressed under diabetic and non-diabetic conditions. To the best of our knowledge, no published study has investigated the role of SODI in the onset and/or progression of diabetic neuropathy. Mutations of SODI have long been associated with the inherited form of amyotrophic lateral sclerosis (ALS) [42] and the theory of oxidative stress-based aging [43]. Early reports indicate that knockout of the SODI gene does not affect nervous system development [44], although recovery following injury is slow and incomplete [45,46]. With respect to diabetes, SODI KO accelerates the development of diabetic nephropathy [47] and cataract formation [48]. Thus, examining the SODI KO mouse as a model of diabetic neuropathy would be a reasonable follow-up study. One limitation of the current approach using literature mining technology is incorrect r missed identification of the mentioned targets within the literature. Based on a performance evaluation using a standard text set BioCreAtlvE (Critical Assessment of Information Extraction systems in Biology) version 2 [49], SciMiner achieved 87. 1% recall (percentage identification of targets in the given text), 71. 3% precision (percentage accuracy of identified target) and 75. 8% F-measure (harmonious average of recall and precision = (2 x recall x precision)/(recall + precision)) before manual revision [14]. In order to improve the accuracy of SciMiner’s results, each target was anually reviewed and corrected by checking the sentences in which each target was identified. Approximately, 120 targets (†10% of the initially identified targets from the ROS-diabetes papers) were removed during the manual review process. The overall accuracy is expected to improve through the review process; however, the review process did not address targets missed by SciMiner, since we did not thoroughly review individual papers. Instead, 5 missed targets, whose associations with ROS-diabetes literature were available in the NCBI Gene2PubMed database, were added to the final ROS-diabetes target list (Additional File 2). How to cite Literature-based discovery of diabetes, Papers

Corruption society free essay sample

News writing Youve gathered the information, done the reporting. Youve interviewed all the people involved, the eye witnesses to the explosion, the police, etc, etc. And now you have to write the story. You have pages in your notebook of facts, observations, quotes. You may have some agency copy, some material from other media. The first thing to do is stop and think. Do not start writing until you have a plan. Read through all your notes, marking the most important pieces of information and the quotes you want to use. The information you have gathered will not have entered your notebook in order of importance. You need to decide what is more important, what is less important, to establish a hierarchy of pieces of information. And this is where you must think about your audience. Not necessarily what interests you most, but what will interest them. It may not be the same thing, and this is where knowing, having a feeling for, understanding your audience is so important. As you stare at the blank screen try to imagine the reader. It depends on the publication you are writing for, of course. You can assume more knowledge if you are writing for a specialist publication, or a specialist section of a newspaper. A cricket report or commentary can assume knowledge of the rules of cricket; an article for a motoring magazine can assume the reader knows what a supercar is. But some specialist publications set out to educate computer magazines are a good example and while interest can be assumed, knowledge of how to use specific pieces of software cannot. So understand the intentions of the publication you write for, or if you are a freelance you seek to sell to. The market sector in which the newspaper is located is also relevant to how you write. You will find longer sentences and paragraphs and sometimes longer words in the more serious newspapers selling relatively small numbers of copies than in mass-selling newspapers with circulations 10 times as big. The reader of the Guardian will tend to be better educated and to have a larger vocabulary than the reader of the Sun. But do not, as a writer, show off your extensive vocabulary. It is never better, wherever you are writing, to prefer the less familiar word wordy is always better than prolix. Nobody is impressed by the use of a word they do not understand or would not use in everyday speech. The danger of talking down to the audience assuming vocabulary as well as knowledge is that it insults readers, makes them feel inadequate.  And that turns them off and, worse, turns them away. They do not read on, and you have not communicated with them. The best writing for popular journalism is some of the best writing in journalism, and is hard to do. It is readily understandable, instantly readable and, if it is done well, makes you want to read on. Space is always the most precious commodity in a newspaper. Long words and sentences take up more space. Self-indulgent writing pleases nobody except perhaps the writer. Stephen King, who has sold more novels than most, reflected on his craft in On Writing, and drew a similar message: One of the really bad things you can do to your writing is to dress up the vocabulary, looking for long words because youre maybe a little bit ashamed of your short ones. This is like dressing up a household pet in evening clothes. The pet is embarrassed and the person who committed this act of premeditated cuteness should be even more embarrassed. So the overriding message in journalistic writing is: Keep It Simple. One of the greatest editors and journalists is Harold Evans, who has written one of the best books on journalistic writing, Essential English for Journalists, Editors and Writers. He summed it up thus: It is not enough to get the news. We must be able to put it across. Meaning must be unmistakable, and it must also be succinct. Readers have not the time and newspapers have not the space for elaborate reiteration. This imposes decisive requirements. In protecting the reader from incomprehension and boredom, the text editor has to insist on language which is specific, emphatic and concise. Every word must be understood by the ordinary reader, every sentence must be clear at one glance, and every story must say something about people. There must never be a doubt about its relevance to our daily life. There must be no abstractions. Below are a series of tips for keeping things simple and encouraging the reader to read it. They are addressed at news writing, but most apply to all forms of journalistic writing. The intro This is the start of the story, the opening paragraph. The traditional news introductory paragraph, still the dominant form, has two related purposes: to engage the reader instantly and to summarise what the story is all about. The structure is known as the inverted pyramid and dates back to the days of hot metal when words on their way on to paper passed through a stage of being slugs of lead. It was always easier and faster to cut a story from the  bottom, using a pair of tweezers. News stories always have to be cut because reporters write them too long, and the (imperfect) theory was that a well structured story could always be cut from the bottom so that in extremis (do not use see later) if the intro was the only paragraph left it still made sense. The good intro depends on your judgment and decisiveness. It declares why the story is being published, what is the newest, most interesting, most important, most significant, most attention-grabbing aspect of the story. It is not a summary of everything yet to come. The best intro will contain a maximum of two or three facts, maybe only one. In a popular tabloid it will consist of one sentence, probably no more than 25 words. The worst intro will be uncertain of what the story is all about and will contain several ideas. The best intro will demand that you read on. The worst will make it likely that you will move on. As Tony Harcup puts it in his Journalism, Principles and Practice: The intro is crucial because it sets the tone for what follows. A poorly written intro might confuse, mislead or simply bore the reader a well-written intro will encourage the reader to stay with you on the strength of the information and angle you have started with. Rest of the story Once youve got the intro right, the second paragraph will be the most important you write. And so on. Holding the readers interest does not stop until he or she has read to the end. You have already planned your structure, the hierarchy of information. After the intro you are amplifying the story, adding new, if subordinate, information, providing detail, explanation and quotes. And doing all this so that the story reads smoothly and seamlessly. News stories are about providing information, and there is nothing more frustrating for the reader that finishing a story with unanswered questions still hanging. Journalism students are taught about the five Ws: who, what, when, where and why. They are a useful tool to check you have covered all the bases, though not all will always apply. It is always difficult to detach yourself from your own prose when you read it through, but try. Try to put yourself in the place of the reader coming cold to the story, interested in it and asking the questions that will make it clear. Have you dealt with them? The subeditor, or text editor, will soon tell you if you havent. There is always a problem over how much knowledge to assume,  particularly with a running story of which todays is another episode. You cannot always start from the beginning for the benefit of reader recently arrived from Mars, but you can include sufficient to ensure it is not meaningless. It is a matter of judgement. Active not passive Always prefer the active tense in news writing, and particularly in intros. The active tense is faster and more immediate; it also uses fewer words. Arsenal were beaten by Manchester United last night is slower than Manchester United beat Arsenal , and if it is a London newspaper Arsenal lost to Manchester United is still preferable. Positive even if it is negative Not: The government has decided not to introduce the planned tax increase on petrol and diesel this autumn. But: The government has abandoned plans to raise fuel taxes this autumn. News is more engaging if it describes something that is happening, rather than something that is not. Quotes Long quotes bring a story grinding to a halt, particularly if they are from politicians, particularly local politicians, bureaucrats or bores. Short, incisive, direct quotes change the pace of a story, add colour and character, illustrate bald facts, and introduce personal experience. Journalists paraphrase speeches and reports to focus on the main points, and to make them shorter and more comprehensible. It is a vital skill, as is using indirect quotation. But a quote will add a different tone of voice, inject emotion or passion, answer the question what was it like?, how did you feel?, what are you going to do next?, what actually happened. Usually the reporter was not there and is gathering the information after the event. The direct quote provides actuality. And sometimes the quote has to be there to provide the precision, when the actual words used are crucial, and sometimes the story itself. Never use a word other than said when attributing a quote. Affirmed, opined, exclaimed, interjected, asserted, declared, are all tacky synonyms which do nothing to help the flow of the story. When people speak they say. On rare occasions it might be relevant to the story if they shout or scream; in which case break the rule. Officialese Language used in letters from bank managers, council officers, utilities and read from their notebooks by police officers giving evidence in court should always be avoided. People do not proceed; they walk. Police do not apprehend; they stop or arrest or detain. At this point in time is now. George Orwell, in his essay Politics and the English Language, converts a passage from Ecclesiastes and turns it into officialese to make the point. Original: I returned, and saw under the sun, that the race is not to the swift, not the battle to the strong, neither yet bread to the wise, nor yet riches to men of understanding, nor yet favour to men of skill; but time and chance happeneth to them all. Orwells rewrite: Objective consideration of contemporary phenomena compels the conclusion that success or failure in competitive activities exhibits no tendency to be commensurate with innate capacity, but that a considerable element of the unpredictable must invariably be taken into account. Adjectives Keith Waterhouse, the veteran Daily Mail and Daily Mirror columnist wrote an irresistible book on journalistic writing called Newspaper Style. It was in fact an adaptation of the Mirror style book he had been commissioned to write. In it he warns of the dangers of adjectives thus: Adjectives should not be allowed in newspapers unless they have something to say. An adjective should not raise questions in the readers mind, it should answer them. Angry informs. Tall invites the question, how tall? The well-worn phrase: his expensive tastes ran to fast cars simply whets the appetite for examples of the expensive tastes and the makes and engine capacity of the fast cars. This test should be applied to all adjectives used in journalistic writing. If they add relevantly to the information being provided, they can stay. If not, strike them. Too many writers believe adjectives add colour and style. Vague or general ones add nothing. Use specific words (red and blue), says Waterhouse, not general ones (brightly coloured). Jargon, abbreviations, acronyms and know-all foreign phrases All of us who work in organisations, professions, specific industries or bureaucracies are surrounded by jargon. We may regard it as shorthand to speed communication because we share the understanding of what it means, but, whether intentional or not, it is a protective shield that excludes those not in the know. That is the effect it  has when used in newspaper writing. Those in the know understand; the rest do not. Anything readers do not understand makes them feel left out rather than included and turns them against the story. They may well stop reading. Medical, scientific and economic terms are a case in point. Avoid them or explain them. Price/earnings ratios and capitalisation mean nothing to the general reader. It is the same with abbreviations and acronyms. Todays students have no idea what CBI stands for; they are more likely to know FoI. A few could expand Nato, fewer the TUC. Many of the terms, although still in use, are generational. They need to be spelt out or explained, or another reader is lost. Just as long words speak down to those with a smaller vocabulary and there is always a simpler, and less space consuming, alternative so well-used Latin expressions mean nothing to those who have not learned that language, apart from lawyers who have had to mug up. Pro bono, inter alia and in extremis have no place in newspapers, and usually mean the writer is showing off. Puns and cliches Headline writers love puns and phrases from 60s pop lyrics and editors frequently have to restrain their use. They sit even less easily in copy, where only readers over 55 can identify. Again, the danger is excluding readers. Worst of all is the extended metaphor or pun. Like this (real) one: Kingsbridge Silver Band has hit a high note with National Lottery chiefs to the tune of nearly  £52,000. Tired old instruments struck a chord with the lottery board, which has drummed up enough cash for a complete new set, giving the band plenty to trumpet about. Yes, really. Apostrophes The printed word has done more to save the apostrophe than the whole of the teaching profession. Given the pace of newspaper and magazine production it is extraordinary that so few errors in spelling or punctuation appear, a tribute to the subeditors who prepare copy for publication. From advertising (shockingly, sometimes intentionally) to the greengrocers board we are bombarded with mis- (and missing) punctuation, yet it is invariably correct in print, though seldom when it emerges from the home printer. If in doubt, and most people are, consult Lynne Truss (Eats, Shoots and Leaves). Often. Exercise: acronyms What do the following acronyms stand for? If you dont know instantly, then you can be sure there will be plenty of readers who dont. So do not use them without explanation. Defra, Asbo, OECD, SEO; CBI; ISA; Fifa; PCT; Sats; FTSE Answers: Department for Environment, Food and Rural Affairs; Anti-Social Behaviour Order; Organisation for Economic Cooperation and Development; Search Engine Optimisation; Confederation of British Industry; Individual Savings Account; Fà ©dà ©ration Internationale de Football Association; Primary Care Trust; Standard Assessment Tests; Financial Times Stock Exchange (used to describe stock market indices such as FTSE 100). Exercise: plain English Rewrite the following two paragraphs in plain English suitable for publication in a newspaper or magazine. Remove unnecessary words, passive verbs, repetition, cliche, jargon and pompous or pretentious expression. Jot down some questions the story fails to answer. Joseph Foster and his sibling Kate were advancing cheerfully along Wesley Street when they were in minor collision with an HGV which unexpectedly mounted the pavement. It transpired later, when the multi-coloured Volvo truck driver who was transporting a container containing motor parts to Oxford was being interviewed by a local radio reporter, that the lorry veered to avoid a police car speeding towards him on the wrong side of the road. The spokesman at police headquarters told a different story. But it was the childrens lucky day as they escaped shocked but unscathed. A hospital spokesman at nearby Eddington hospital, run by the Barton NHS Foundation Trust, said the two children were lucky not to have been seriously injured. As it was, declared Andrew Brown, they were examined in A and E and allowed to go home. Unfortunately Kates buggy was beyond repair.'