Unleashing the full power of LHCb to probe stealth new physics.

In this paper, we describe the potential of the LHCb experiment to detect stealth physics. This refers to dynamics beyond the standard model that would elude searches that focus on energetic objects or precision measurements of known processes. Stealth signatures include long-lived particles and light resonances that are produced very rarely or together with overwhelming backgrounds. We will discuss why LHCb is equipped to discover this kind of physics at the Large Hadron Collider and provide examples of well-motivated theoretical models that can be probed with great detail at the experiment.

Segregation of four Agrobacterium tumefaciens replicons during polar growth: PopZ and PodJ control segregation of essential replicons.

Agrobacterium tumefaciens C58 contains four replicons, circular chromosome (CC), linear chromosome (LC), cryptic plasmid (pAt), and tumor-inducing plasmid (pTi), and grows by polar growth from a single growth pole (GP), while the old cell compartment and its old pole (OP) do not elongate. We monitored the replication and segregation of these four genetic elements during polar growth. The three largest replicons (CC, LC, pAt) reside in the OP compartment prior to replication; post replication one copy migrates to the GP prior to division. CC resides at a fixed location at the OP and replicates first. LC does not stay fixed at the OP once the cell cycle begins and replicates from varied locations 20 min later than CC. pAt localizes similarly to LC prior to replication, but replicates before the LC and after the CC. pTi does not have a fixed location, and post replication it segregates randomly throughout old and new cell compartments, while undergoing one to three rounds of replication during a single cell cycle. Segregation of the CC and LC is dependent on the GP and OP identity factors PopZ and PodJ, respectively. Without PopZ, replicated CC and LC do not efficiently partition, resulting in sibling cells without CC or LC. Without PodJ, the CC and LC exhibit abnormal localization to the GP at the beginning of the cell cycle and replicate from this position. These data reveal PodJ plays an essential role in CC and LC tethering to the OP during early stages of polar growth.

GROWTH POLE RING protein forms a 200-nm-diameter ring structure essential for polar growth and rod shape in Agrobacterium tumefaciens.

Polar growth in Agrobacterium pirates and repurposes well-known bacterial cell cycle proteins, such as FtsZ, FtsA, PopZ, and PodJ. Here we identify a heretofore unknown protein that we name GROWTH POLE RING (GPR) due to its striking localization as a hexameric ring at the growth pole during polar growth. GPR also localizes at the midcell late in the cell cycle just before division, where it is then poised to be precisely localized at new growth poles in sibling cells. GPR is 2,115 aa long, with two N-terminal transmembrane domains placing the bulk of the protein in the cytoplasm, N- and C-terminal proline-rich disordered regions, and a large 1,700-aa central region of continuous α-helical domains. This latter region contains 12 predicted adjacent or overlapping apolipoprotein domains that may function to sequester lipids during polar growth. Stable genetic deletion or riboswitch-controlled depletion results in spherical cells that grow poorly; thus, GPR is essential for wild-type growth and morphology. As GPR has no predicted enzymatic domains and it forms a distinct 200-nm-diameter ring, we propose that GPR is a structural component of an organizing center for peptidoglycan and membrane syntheses critical for cell envelope formation during polar growth. GPR homologs are found in numerous Rhizobiales; thus, our results and proposed model are fundamental to understanding polar growth strategy in a variety of bacterial species.

Determination of MICING: a new assay for assessing minimal inhibitory concentration for invasive growth.

Our work was focused on a new assay for characterising clinically important yeast. This assay was developed due to the need for new diagnostic methods for recognising potentially virulent strains of increasingly important non-albicans yeast pathogens, such as Saccharomyces cerevisiae and Candida glabrata. With the great diversity among strains for virulence and virulence factors, identification to the species level is not sufficient; therefore, testing for specific virulent traits remains the best option. We show here that the proposed assay uncovers the relationships between the three most important yeast virulence traits in a single test: the ability of a strain to invade solid medium, while resisting the presence of an antimycotic and high temperature (37 °C). We combined the quantitative agar invasion assay with classical antimycotic susceptibility testing into a single assay. Similarly to the minimal inhibitory concentration (MIC) value, we defined the MICING (minimal inhibitory concentration of antimycotic for invasive growth) as the concentration of an antimycotic above which the yeast invasive growth is significantly repressed. In this study, we tested three of the most common antimycotics: fluconazole, itraconazole and amphotericin B. The response of yeast strains invasion was characteristic of each antimycotic, indicating their mechanisms of action. In addition to MICING, the assay provides quantitative information about the superficial and invasive growth, and also about the relative invasion, which helps in identifying clinically important yeast, such as azole-resistant and/or invasive strains of S. cerevisiae and C. glabrata.

Topical formulations of metaflumizone plus amitraz to treat flea and tick infestations on dogs.

A topical spot-on solution was developed for treating pets that contained of active ingredients metaflumizone and amitraz and intended for use as an ectoparasiticide. The formulation vehicle system was designed by balancing the following three attributes of various solvents: evaporation/drying, surface spreading, and percutaneous absorption. The solvents were selected by evaluating the solubilization capacity of individual solvents with respect to the above active ingredients. The evaporation rates of various solvent systems were then determined. The visual observations of the treatment sites was also performed a day after treating the dogs to understand the cosmetic effect of various solvent systems. The lead formulations dried off within a day after application with no noticeable residue at the treatment site, while others produced appreciable powdery residue or a large wet and oily spot. The stability of the lead formulations was also evaluated over 2 years to demonstrate a 2-year shelf life of this product.

Highly compact 2D graphical representation of DNA sequences.

Most 2D graphical representations of primary DNA sequences, while offering visual geometrical patterns for depicting sequences, do require considerable space if enough details of such representations are to be visible. In this contribution, we consider a highly compact graphical representation of DNA, which allows visual inspection and numerical characterization of DNA sequences having a large number of nucleic acid bases. The approach is illustrated on the DNA sequences of the first exon of human beta-globin. The same graphical approach not only allows one to depict differences in composition within a single DNA, but makes possible graphical representation of protein sequences, which have hitherto evaded similar 2D visual representations.

Topical umbilical cord care at birth.

BACKGROUND: Umbilical cord infection caused many neonatal deaths before aseptic techniques were used. OBJECTIVES: To assess the effects of topical cord care in preventing cord infection, illness and death. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (September 2003) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003). We also contacted experts in the field. SELECTION CRITERIA: Randomized and quasi-randomized trials of topical cord care compared with no topical care, and comparisons between different forms of care. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trial quality and extracted data. MAIN RESULTS: Twenty-one studies (8959 participants) were included, the majority of which were from high-income countries. No systemic infections or deaths were observed in any of the studies reviewed. No difference was demonstrated between cords treated with antiseptics compared with dry cord care or placebo. There was a trend to reduced colonization with antibiotics compared to topical antiseptics and no treatment. Antiseptics prolonged the time to cord separation. Use of antiseptics was associated with a reduction in maternal concern about the cord. REVIEWERS' CONCLUSIONS: Good trials in low-income settings are warranted. In high-income settings, there is limited research which has not shown an advantage of antibiotics or antiseptics over simply keeping the cord clean. Quality of evidence is low.

Prediction of selectivity of alpha1-adrenergic antagonists by counterpropagation neural network (CP-ANN).

A quantitative structure-selectivity relationships of series of structurally diverse alpha1-adrenergic antagonists was performed by using counter-propagation neural network (CP-ANN). The theoretical molecular descriptors have been calculated and selected using CODESSA program. The results obtained for a highly non-congeneric set of molecules have confirmed the potential of use of CP-ANN approach in prediction of relative activity (selectivity) of alpha1-adrenergic antagonists.

Application of counterpropagation artificial neural network for modelling properties of fish antibiotics.

The present study focuses on fish antibiotics which are an important group of pharmaceuticals used in fish farming to treat infections and, until recently, most of them have been exposed to the environment with very little attention. Information about the environmental behaviour and the description of the environmental fate of medical substances are difficult or expensive to obtain. The experimental information in terms of properties is reported when available, in other cases, it is estimated by standard tools as those provided by the United States Environmental Protection Agency EPISuite software and by custom quantitative structure-activity relationship (QSAR) applications. In this study, a QSAR screening of 15 fish antibiotics and 132 xenobiotic molecules was performed with two aims: (i) to develop a model for the estimation of octanol--water partition coefficient (logP) and (ii) to estimate the relative binding affinity to oestrogen receptor (log RBA) using a model constructed on the activities of 132 xenobiotic compounds. The custom models are based on constitutional, topological, electrostatic and quantum chemical descriptors computed by the CODESSA software. Kohonen neural networks (self organising maps) were used to study similarity between the considered chemicals while counter-propagation artificial neural networks were used to estimate the properties.

Perinatal mortality and morbidity in developing countries. A global view.

Global perinatal mortality figures show that of the 132 million births per year, there are between 6 and 7 million perinatal deaths. While 90% of these births are in less developed countries, perinatal deaths take 98% of the global share. These statistics show on average the rates as they were in England during the 1930s. The most common recorded medical causes of perinatal deaths are also similar in the less developed countries, and the common denominators are early childbearing, poor maternal health and above all, the lack of appropriate and quality services. Although life-saving practices for most infants have been known for decades, currently a third of mothers still have no access to services during pregnancy, and almost half do not have access to services for childbirth. There are enormous variations both among and within countries. It takes innovation to find the best fit between the needs of women and infants and resources. A health worker with excellent knowledge and skills is the key resource and the best investment. The cost is moderate, and the investment pays a high dividend in improved health of both the mother and her baby, and better health for the next generation at lower cost.

Application of a Kohonen neural network to the analysis of data regarding the alkylation of toluene with methanol catalyzed by ZSM-5 type zeolites.

para-Xylene is widely used in chemical industry. It can be synthesized by alkylation of toluene with methanol using zeolite ZSM-5 as catalyst. The proportion of para-xylene, among its other isomers and other reaction byproducts, depends on the reaction conditions. As this process still remains largely empirical, we attempted to build a theoretical model able to predict the para-xylene yield under specific reaction conditions. We have consequently collected data regarding this reaction from the literature and exploited the potency of a particular artificial neural network (ANN), the counter-propagation ANN based on the Kohonen technique. The results show that such an approach is suitable to establish a predictive model of the yield in para-xylene on the basis of reaction parameters. The quality of the model could be further improved by considering a larger valuable data set, e.g. including experiments characterized by a low yield in para-xylene.

Novel matrix invariants for characterization of changes of proteomics maps.

Previous studies on mathematical characterization of proteomics maps by sets of map invariants were based on the construction of a set of distance-related matrices obtained by matrix multiplication of a single matrix by itself. Here we consider an alternative characterization of proteomics maps based on a set of matrices characterizing local features of an embedded zigzag curve over the map. It is shown that novel invariants can well characterize proteomics maps. Advantages of the novel approach are discussed.

On 3-D graphical representation of proteomics maps and their numerical characterization.

We consider numerical characterization of proteomics maps by representing a map as a three-dimensional graphical object based on x, y coordinates of the spots and using their relative abundance as the z coordinate. In our representation the protein spots are first ordered based on their relative abundance and labeled accordingly. In the next step a 3-D path is constructed connecting spots having adjacent labels. Finally a matrix is constructed by assigning to each pairs of labels (i, j) matrix element, the numerical value of which is based on the quotients of the Euclidean distance and the distance along the 3-D zigzag between the two points. The approach has been illustrated on a fragment of a proteomics map and compared with 2-D graphical representation of proteomics maps.

Computer simulation of ion chromatography separation: an algorithm enabling continuous monitoring of anion distribution on an ion-exchange chromatography column.

A computer algorithm for the calculation of ion chromatography separation is presented. It is based on the calculation of equilibrium concentrations of present analyte in discrete column segments. The continuous column is treated as a number of discrete cells or segments where the equilibration process between the stationary phase and the eluent is simulated. The ion-exchange equilibration process is supposed to be instantaneous and quantitative. The continuous flow of the eluent is rendered by discrete transfers. The size of each transfer of the eluent corresponds to a portion of the volume contained in one column segment. The equilibrium calculations in all column segments are repeated for each transfer of the eluent, through all the stages of the chromatographic process. The distribution of the analytes between the stationary phase and the eluent can be monitored at any step and in any column segment which means that the described algorithm provides the spatial and time concentration profiles. The simulated chromatogram is acquired as a time-concentration profile in the last column segment. The obtained chromatograms are in good agreement with the experimental ones. The distribution of ions between the stationary phase and the eluent in the early stages of the ion chromatographic process can thus be studied with confidence.

On interpretation of well-known topological indices.

Many topological indices lack an interpretation in terms of simple physicochemical quantities. We have reexamined the structural interpretation of well-known topological indices: the connectivity index (1)chi, the Wiener index W, and the Hosoya topological index Z. We relate the success of various indices in structure-property studies to the degree to which they differentiate contributions from more exposed terminal bonds and more buried interior bonds. When considering bond additive properties of alkanes we find better regressions when greater weights are assigned to terminal CC bonds and lesser weights to internal CC. We suggest here that topological indices be discussed in terms of their partitioning into bond contributions, which for different indices and different bonds will assume different values. With this insight we modified the Wiener index W into a new index W, in which bond contributions are determined using the reciprocal of the product of the number of atoms on each side of a bond. Similarly we modified the Hosoya index Z into Z in which the frequency of occurrence of individual CC bonds in the patterns of disjoint bonds are considered. Novel indices are compared with other indices and they show to yield better regressions for boiling points of octane isomers. This suggests a useful classification of topological indices based on the relative magnitudes of the contributions of terminal and interior bonds. To extend such considerations to other indices one needs to consider partitioning of global molecular indices into bond additive terms. A general scheme for partitioning of molecular descriptors into bond contributions is outlined for indices derived from a selection of matrices associated with molecular graphs.

The N- and C-terminal portions of the Agrobacterium VirB1 protein independently enhance tumorigenesis.

Genetic transformation of plants by Agrobacterium tumefaciens is mediated by a virulence (vir)-specific type IV secretion apparatus assembled from 11 VirB proteins and VirD4. VirB1, targeted to the periplasm by an N-terminal signal peptide, is processed to yield VirB1*, comprising the C-terminal 73 amino acids. The N-terminal segment, which shares homology with chicken egg white lysozyme as well as lytic transglycosylases, may provide local lysis of the peptidoglycan cell wall to create channels for transporter assembly. Synthesis of VirB1* followed by its secretion to the exterior of the cell suggests that VirB1* may also have a role in virulence. In the present study, we provide evidence for the dual roles of VirB1 in tumorigenesis as well as the requirements for processing and secretion of VirB1*. Complementation of a virB1 deletion strain with constructs expressing either the N-terminal lysozyme-homologous region or VirB1* results in tumors intermediate in size between those induced by a wild-type strain and a virB1 deletion strain, suggesting that each domain has a unique role in tumorigenesis. The secretion of VirB1* translationally fused to the signal peptide indicates that processing and secretion are not coupled. When expressed independently of all other vir genes, VirB1 was processed and VirB1* was secreted. When restricted to the cytoplasm by deletion of the signal peptide, VirB1 was neither processed nor secreted and did not restore virulence to the virB1 deletion strain. Thus, factors that mediate processing of VirB1 and secretion of VirB1* are localized in the periplasm or outer membrane and are not subject to vir regulation.

Topical umbilical cord care at birth.

BACKGROUND: Umbilical cord infection caused many neonatal deaths before aseptic techniques were used. OBJECTIVES: The objective of this review was to assess the effects of topical cord care in preventing cord infection, illness and death. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register (Cochrane Library issue 4, 1997) and Medline. We also contacted experts in the field. SELECTION CRITERIA: Randomised and quasi-randomised trials of topical cord care compared with no routine care, and comparisons between different forms of care. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trial quality and extracted data. MAIN RESULTS: Ten studies were included, all from developed countries. No systemic infections or deaths were observed in any of the studies reviewed. Cord and other skin infections within six weeks of observation were not affected by use of antiseptics. There was a trend to reduced colonization with antibiotics compared to antiseptics and no treatment. Antiseptics prolonged the time to cord separation. Use of antiseptics was associated with a reduction in maternal concern about the cord. REVIEWER'S CONCLUSIONS: Simply keeping the cord clean appears to be as effective and safe as using antibiotics or antiseptics.

Viscosity prediction of lipophilic semisolid emulsion systems by neural network modelling.

Previously published data (Gasperlin et al., 1998) on viscoelastic behaviour of lipophilic semisolid emulsion systems and the prediction of their physical stability by neural network modelling are analysed in further detail. Most attention has been paid to viscosity, which with storage (G') and loss modulus (G"), is one of the most important rheological parameters influenced by structure. Complex dynamic viscosity (eta*) was measured by oscillatory rheometry. The viscosity dependence of the lipophilic semisolid emulsions on the ratio of the particular components was defined by the neural network (error back-propagation algorithm), linear and incomplete polynomial models of higher orders. Polynomial models were used to complement the neural network model and to determine the relationship between variables. Since the viscosity was expressed in the whole measured frequency range, modelling was more complex and indirect modelling was introduced. The determined models were tested and the results confirm their usefulness for the explanation and prediction of the rheological characteristics of emulsion systems. The trained and tested neural network model proved to be a highly effective and applicable tool for predicting the viscosity of a lipophilic semisolid emulsion system of given composition.