A branch-and-bound methodology within algebraic modelling systems

Through the use of application-specific branch-and-bound directives it is possible to find solutions to combinatorial models that would otherwise be difficult or impossible to find by just using generic branch-and-bound techniques within the framework of mathematical programming. {\sc Minto} is an example of a system which offers the possibility to incorporate user-provided directives (written in {\sc C}) to guide the branch-and-bound search. Its main focus, however, remains on mathematical programming models. The aim of this paper is to present a branch-and-bound methodology for particular combinatorial structures to be embedded inside an algebraic modelling language. One advantage is the increased scope of application. Another advantage is that directives are more easily implemented at the modelling level than at the programming level

Best data-dependent triangulations

AbstractWhen reconstructing a surface from irregularly spaced data we need to decide how to identify a good triangulation. As a measure of quality we consider various differential geometrical properties, namely integral absolute Gaussian curvature, integral absolute mean curvature and area. A comparison is made with data-dependent triangulation methods that exist in the literature

Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism

Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonised by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonisation to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc) on this response at the transcriptional, physiological and metabolic levels. Galactose (Gal), N-acetylglucosamine (GlcNAc) and mannose (Man) affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo 13C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed) and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s) was readily consumed and elicited a metabolic shift towards a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome). In central carbon metabolism (most represented category), Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence

Managing children with daytime urinary incontinence:a survey of Dutch general practitioners

Background: In the Netherlands, parents of children with daytime urinary incontinence (UI) first consult general practitioners (GPs). However, GPs need more specific guidelines for daytime UI management, resulting in care and referral decisions being made without clear guidance.Objectives: We aimed to identify Dutch GP considerations when treating and referring a child with daytime UI.Methods: We invited GPs who referred at least one child aged 4–18 years with daytime UI to secondary care. They were asked to complete a questionnaire about the referred child and the management of daytime UI in general.Results: Of 244 distributed questionnaires, 118 (48.4%) were returned by 94 GPs. Most reported taking a history and performing basic diagnostic tests like urine tests (61.0%) and physical examinations (49.2%) before referral. Treatment mostly involved lifestyle advice, with only 17.8% starting medication. Referrals were usually at the explicit wish of the child/parent (44.9%) or because of symptom persistence despite treatment (39.0%). GPs usually referred children to a paediatrician (n = 99, 83.9%), only referring to a urologist in specific situations. Almost half (41.4%) of the GPs did not feel competent to treat children with daytime UI and more than half (55.7%) wanted a clinical practice guideline. In the discussion, we explore the generalisability of our findings to other countries.Conclusion: GPs usually refer children with daytime UI to a paediatrician after a basic diagnostic assessment, usually without offering treatment. Parental or child demand is the primary stimulus for referral.</p

Rangelands Vegetation Mapping at Species Composition Level Using the \u3cb\u3eSPiCla\u3c/b\u3e Method: \u3cb\u3eS\u3c/b\u3eDM Based \u3cb\u3ePi\u3c/b\u3exel \u3cb\u3eCla\u3c/b\u3essification and Fuzzy Accuracy. A New Approach of Map Making

Vegetation maps have been made since centuries. The vegetation cover was represented as homogeneous mapping units (polygons), representing different vegetation types, where each type consists a combination of different plant species (floristic composition). More recent, with the use of satellite imagery, the polygons have been replaced by pixels with similar content as the polygon maps. In both approaches, field-observations were linked to the mapping units (polygons or pixels) often resulting in a complex of different vegetation types per mapping unit. In our new approach field data (sample points) on presence and abundance of individual grass species are spatially extrapolated based on a set of environmental layers, using the species distribution modelling approach (SDM). When combined, each pixel will contain its own set of information about the vegetation structure and its floristic composition. This new methodology (SPiCla) results in a very accurate and detailed vegetation map at pixel level, allowing extraction of very detailed, accurate and easy to update spatial information on e.g., forage production and quality (palatability) for rangelands management. As no exact boundaries exist, but only gradients, we introduced fuzzy accuracy. The resolution mainly depends on the resolution of (or one of) the environmental layers used, scale of interest and workability. The methodology is generic and applicable to any other region in the world

Specificity, duplex degradation and subcellular localization of antagomirs

MicroRNAs (miRNAs) are an abundant class of 20–23-nt long regulators of gene expression. The study of miRNA function in mice and potential therapeutic approaches largely depend on modified oligonucleotides. We recently demonstrated silencing miRNA function in mice using chemically modified and cholesterol-conjugated RNAs termed ‘antagomirs’. Here, we further characterize the properties and function of antagomirs in mice. We demonstrate that antagomirs harbor optimized phosphorothioate modifications, require >19-nt length for highest efficiency and can discriminate between single nucleotide mismatches of the targeted miRNA. Degradation of different chemically protected miRNA/antagomir duplexes in mouse livers and localization of antagomirs in a cytosolic compartment that is distinct from processing (P)-bodies indicates a degradation mechanism independent of the RNA interference (RNAi) pathway. Finally, we show that antagomirs, although incapable of silencing miRNAs in the central nervous system (CNS) when injected systemically, efficiently target miRNAs when injected locally into the mouse cortex. Our data further validate the effectiveness of antagomirs in vivo and should facilitate future studies to silence miRNAs for functional analysis and in clinically relevant settings

Complex polar machinery required for proper chromosome segregation in vegetative and sporulating cells of Bacillus subtilis

Chromosome segregation is an essential process of cell multiplication. In prokaryotes, segregation starts with the newly replicated sister origins of replication, oriCs, which move apart to defined positions in the cell. We have developed a genetic screen to identify mutants defective in placement of oriC during spore development in the Gram-positive bacterium Bacillus subtilis. In addition to the previously identified proteins Soj and DivIVA, our screen identified several new factors involved in polar recruitment of oriC: a reported regulator of competence ComN, and the regulators of division site selection MinD and MinJ. Previous work implicated Soj as an important regulator of oriC positioning in the cell. Our results suggest a model in which the DivIVA-interacting proteins ComN and MinJ recruit MinD to the cell pole, and that these proteins work upstream of Soj to enable oriC placement. We show that these proteins form a polar complex, which acts in parallel with but distinct from the sporulation-specific RacA pathway of oriC placement, and also functions during vegetative growth. Our study further shows that MinD has two distinct cell cycle roles, in cell division and chromosome segregation, and highlights that cell probably use multiple parallel mechanisms to ensure accurate chromosome segregation.</p

Dispatched Homolog 2 is targeted by miR-214 through a combination of three weak microRNA recognition sites

MicroRNAs (miRNAs) regulate gene expression by inhibiting translation of target mRNAs through pairing with miRNA recognition elements (MREs), usually in 3′ UTRs. Because pairing is imperfect, identification of bona fide mRNA targets presents a challenge. Most target recognition algorithms strongly emphasize pairing between nucleotides 2–8 of the miRNA (the ‘seed’ sequence) and the mRNA but adjacent sequences and the local context of the 3′ UTR also affect targeting. Here, we show that dispatched 2 is a target of miR-214. In zebrafish, dispatched 2 is expressed in the telencephalon and ventral hindbrain and is essential for normal zebrafish development. Regulation of dispatched 2 by miR-214 is via pairing with three, noncanonical, weak MREs. By comparing the repression capacity of GFP reporters containing different dispatched 2 sequences, we found that a combination of weak sites, which lack canonical seed pairing, can effectively target an mRNA for silencing. This finding underscores the challenge that prediction algorithms face and emphasizes the need to experimentally validate predicted MREs