Annotation of the modular polyketide synthase and nonribosomal peptide synthetase gene clusters in the genome of Streptomyces tsukubaensis NRRL18488

et al.The high G+C content and large genome size make the sequencing and assembly of Streptomyces genomes more difficult than for other bacteria. Many pharmaceutically important natural products are synthesized by modular polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs). The analysis of such gene clusters is difficult if the genome sequence is not of the highest quality, because clusters can be distributed over several contigs, and sequencing errors can introduce apparent frameshifts into the large PKS and NRPS proteins. An additional problem is that the modular nature of the clusters results in the presence of imperfect repeats, which may cause assembly errors. The genome sequence of Streptomyces tsukubaensis NRRL18488 was scanned for potential PKS and NRPS modular clusters. A phylogenetic approach was used to identify multiple contigs belonging to the same cluster. Four PKS clusters and six NRPS clusters were identified. Contigs containing cluster sequences were analyzed in detail by using the ClustScan program, which suggested the order and orientation of the contigs. The sequencing of the appropriate PCR products confirmed the ordering and allowed the correction of apparent frameshifts resulting from sequencing errors. The product chemistry of such correctly assembled clusters could also be predicted. The analysis of one PKS cluster showed that it should produce a bafilomycin-like compound, and reverse transcription (RT)-PCR was used to show that the cluster was transcribed. © 2012, American Society for Microbiology.We thank the Government of Slovenia, Ministry of Higher Education, Science and Technology (Slovenian Research Agency [ARRS]), for the award of grant no. J4-9331 and L4-2188 to H.P. We also thank the Ministry of the Economy, the JAPTI Agency, and the European Social Fund (contract no. 102/2008) for the funds awarded for the employment of G.K. This work was also funded by a cooperation grant of the German Academic Exchange Service (DAAD) and the Ministry of Science, Education, and Sports, Republic of Croatia (to J.C. and D.H.), and by grant 09/5 (to D.H.) from the Croatian Science Foundation.Peer Reviewe

Machine Learning in Automated Text Categorization

The automated categorization (or classification) of texts into predefined categories has witnessed a booming interest in the last ten years, due to the increased availability of documents in digital form and the ensuing need to organize them. In the research community the dominant approach to this problem is based on machine learning techniques: a general inductive process automatically builds a classifier by learning, from a set of preclassified documents, the characteristics of the categories. The advantages of this approach over the knowledge engineering approach (consisting in the manual definition of a classifier by domain experts) are a very good effectiveness, considerable savings in terms of expert manpower, and straightforward portability to different domains. This survey discusses the main approaches to text categorization that fall within the machine learning paradigm. We will discuss in detail issues pertaining to three different problems, namely document representation, classifier construction, and classifier evaluation.Comment: Accepted for publication on ACM Computing Survey

Diabetic gastroparesis: Therapeutic options

Gastroparesis is a condition characterized by delayed gastric emptying and the most common known underlying cause is diabetes mellitus. Symptoms include nausea, vomiting, abdominal fullness, and early satiety, which impact to varying degrees on the patient’s quality of life. Symptoms and deficits do not necessarily relate to each other, hence despite significant abnormalities in gastric emptying, some individuals have only minimal symptoms and, conversely, severe symptoms do not always relate to measures of gastric emptying. Prokinetic agents such as metoclopramide, domperidone, and erythromycin enhance gastric motility and have remained the mainstay of treatment for several decades, despite unwanted side effects and numerous drug interactions. Mechanical therapies such as endoscopic pyloric botulinum toxin injection, gastric electrical stimulation, and gastrostomy or jejunostomy are used in intractable diabetic gastroparesis (DG), refractory to prokinetic therapies. Mitemcinal and TZP-101 are novel investigational motilin receptor and ghrelin agonists, respectively, and show promise in the treatment of DG. The aim of this review is to provide an update on prokinetic and mechanical therapies in the treatment of DG

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Could Active Perception Aid Navigation of Partially Observable Grid Worlds?

Due to the unavoidable fact that a robot&apos;s sensors will be limited in some manner, it is entirely possible that it can find itself unable to distinguish between di#ering states of the world (the world is in e#ect partially observable). If reinforcement learning is used to train the robot, then this confounding of states can have a serious e#ect on its ability to learn optimal and stable policies. Good results have been achieved by enhancing reinforcement learning algorithms through the addition of memory or the use of internal models. In our work we take a di#erent approach and consider whether active perception could be used instead

Custom interfaces for advanced queries in search engines

Those seeking information from the Internet often start from a search engine, using either its organised directory structure or its text query facility. In response to the difficulty in identifying the most relevant pages for some information needs, many search engines offer Boolean text matching and some, including Google, AltaVista and HotBot, offer the facility to integrate additional information into a more advanced request. Amongst web users, however, it is known that the employment of complex enquiries is far from universal, with very short queries being the norm. It is demonstrated that the gap between the provision of advanced search facilities and their use can be bridged, for specific information needs, by the construction of a simple interface in the form of a website that automatically formulates the necessary requests. It is argued that this kind of resource, perhaps employing additional knowledge domain specific information, is one that could be useful for websites or portals of common interest groups. The approach is illustrated by a website that enables a user to search the individual websites of university level institutions in European Union associated countries

Search Engine-Crawler Symbiosis: Adapting to Community Interests

Web crawlers have been used for nearly a decade as a search engine component to create and update large collections of documents