Isolation by genomic subtraction of subspecies-specific DNA probes from Verticillium dahliae

The vascular wilt pathogen Verticillium dahliae Kleb. has a very broad host range, including more than 200 different plant species in 45 families. Most isolates cannot be discriminated morphologically, and reliable, rapid methods for classifying and differentiating strains are needed. We have used a genomic subtraction method to isolate DNA probes that can be used to differentiate V. dahliae isolates and to investigate the genetic variation within this fungal species

Limited Activity Of Miltefosine In Murine Models Of Cryptococcal Meningoencephalitis And Disseminated Cryptococcosis

Miltefosine is an alkyl phosphocholine with good oral bioavailability and in vitro activity against Cryptococcus species that has gained interest as an additional agent for cryptococcal infections. Our objective was to further evaluate the in vivo efficacy of miltefosine in experimental in vivo models of cryptococcal meningoencephalitis and disseminated cryptococcosis. Mice were infected intracranially or intravenously with either C. neoformans USC1597 or H99. Miltefosine treatment (1.8 to 45 mg/kg of body weight orally once daily) began at either 1 h or 1 day postinoculation. Fluconazole (10 mg/kg orally twice daily) or amphotericin B deoxycholate (3 mg/kg intraperitoneally once daily) served as positive controls. In our standard models, miltefosine did not result in significant improvements in survival or reductions in fungal burden against either C. neoformans isolate. There was a trend toward improved survival with miltefosine at 7.2 mg/kg against disseminated cryptococcosis with the H99 strain but only at a low infecting inoculum. In contrast, both fluconazole and amphotericin B significantly improved survival in mice with cryptococcal meningoencephalitis and disseminated cryptococcosis due to USC1597. Amphotericin B also improved survival against both cryptococcal infections caused by H99. Combination therapy with miltefosine demonstrated neither synergy nor antagonism in both models. These results demonstrate limited efficacy of miltefosine and suggest caution with the potential use of this agent for the treatment of C. neoformans infections.Pharmac

The Formation of a Cross-Selling Initiative Climate and its Interplay with Service Climate

Purpose— This study explores the formation and consequences of a cross-selling initiative climate, as well as how a service climate, which provides an important boundary condition, affects both its formation and its ultimate impact on service–sales performance. This article identifies two important predictors of a cross-selling initiative climate: frontline employees’ perceptions of supervisors’ bottom-line mentality and their own sense of accountability. Design/methodology/approach— The multilevel data set includes 180 frontline staff and supervisors (team leaders) from 31 teams employed by a spa/beauty salon chain. Hierarchical linear modelling and partial least squares methods serve to analyse the data. Findings— Supervisors’ bottom-line mentality disrupts a cross-selling initiative climate; a sense of accountability exerts a positive impact, at both individual and team levels. A service climate at the team level weakens the impact of a sense of accountability on a cross-selling initiative climate. A cross-selling initiative climate has a positive effect on team-level service–sales performance, but this effect is weakened by the service climate. Originality/value— This study conceptualises an important frontline work unit attribute as a climate. It offers an initial argument that a cross-selling initiative climate is a central factor driving a work unit’s service–sales performance, which can increase firms’ productivity and competitive advantages. With this initial attempt to explore the antecedents and consequences of a cross-selling initiative climate, the study also offers novel insights into the interplay between a service and a cross-selling initiative climate

CC Sculptoris: A superhumping intermediate polar

We present high speed optical, spectroscopic and Swift X-ray observations made during the dwarf nova superoutburst of CC Scl in November 2011. An orbital period of 1.383 h and superhump period of 1.443 h were measured, but the principal new finding is that CC Scl is a previously unrecognised intermediate polar, with a white dwarf spin period of 389.49 s which is seen in both optical and Swift X-ray light curves only during the outburst. In this it closely resembles the old nova GK Per, but unlike the latter has one of the shortest orbital periods among intermediate polars.Comment: Accepted for publication in MNRAS; 11 pages, 19 figure

Minor structural modifications to alchemix influence mechanism of action and pharmacological activity

Alchemix is an exemplar of a class of anthraquinone with efficacy against multidrug resistant tumors. We have explored further the mechanism of action of alchemix and investigated the effect of extending its side arm bearing the alkylating functionality with regard to DNA binding and activity against multidrug resistant cancer cells. Increasing the distance between the intercalating chromophore and the alkylating functionality of ICT2901 (propyl), ICT2902 (butyl) and ICT2903 (pentyl), led to a higher number of DNA alkylation sites, more potent topoisomerase II inhibition and generated more apoptotic and necrotic cells when analysed in p53-proficient HCT116 cells. Intriguingly, alchemix, the compound with the shortest distance between its intercalative chromophore and alkylating functionality (ethyl), did not conform to this SAR. A different toxicity pattern against DNA repair defective CHO cell lines as well as arrest of cells in G1 supports a somewhat distinct mode of action by alchemix compared with its analogues. Importantly, both alchemix and ICT2901 demonstrated greater cytotoxic activity against anthraquinone-resistant MCF-7/adr cells than wild-type MCF-7 cells. Subtle synthetic modification in this anthraquinone series has led to significant changes to the stability of DNA-compound complexes and cellular activity. Given that the failure of chemotherapy in the clinic is often associated with MDR, the results of both alchemix and ICT2901 represent important advances towards improved therapies

Mathematical study of the effects of applied stress, T-stress and back stress in photoelastic fringe patterns

This work is an attempt at developing a novel mathematical model to describe the stresses near the crack tip, taking into consideration the effects of plasticity. The focus is on describing how the applied stress normal to the crack, herein referred to as the K-stress, Tstress and ‘back stress’ induced by plasticity along the crack flank and in the crack tip plastic zone influence the crack tip elastic stress fields. The important features emerging from this study are that the sign and magnitude of each term can substantially alter the crack tip stress fields, and hence influence the photoelastic fringe patterns. To validate the mathematical model, polycarbonate compact tension specimens have been used and observed in a transmission polariscope in order to study the single effect of a pure ‘back stress’ (acting as an interfacial shear stress at the elastic-plastic boundary) and combination effects of K-stress, Tstress and ‘back stress’. It is observed that the fringe patterns obtained through experiment show good agreement with those derived by mathematical modelling

Inverse problem of photoelastic fringe mapping using neural networks

This paper presents an enhanced technique for inverse analysis of photoelastic fringes using neural networks to determine the applied load. The technique may be useful in whole-field analysis of photoelastic images obtained due to external loading, which may find application in a variety of specialized areas including robotics and biomedical engineering. The presented technique is easy to implement, does not require much computation and can cope well within slight experimental variations. The technique requires image acquisition, filtering and data extraction, which is then fed to the neural network to provide load as output. This technique can be efficiently implemented for determining the applied load in applications where repeated loading is one of the main considerations. The results presented in this paper demonstrate the novelty of this technique to solve the inverse problem from direct image data. It has been shown that the presented technique offers better result for the inverse photoelastic problems than previously published works

Do Vertebral Chemical Signatures Distinguish Juvenile Blacktip Shark (Carcharhinus limbatus) Nursery Regions in the Northern Gulf of Mexico?

Identifying and protecting shark nurseries is a common management strategy used to help rebuild overfished stocks, yet we know little about connectivity between juvenile and adult populations. By analysing trace metals incorporated into vertebral cartilage, it may be possible to infer natal origin based on nursery-specific chemical signatures. To assess the efficacy of this approach, we collected juvenile blacktip sharks (Carcharhinus limbatus; n = 93) from four regions in the Gulf of Mexico in 2012 and 2013 and analysed their vertebral centra with laser ablation-inductively coupled plasma-mass spectrometry. We observed significant regional differences in six element : Ca ratios in both 2012 and 2013. Multi-element chemical signatures were significantly different among regions and between year-classes. Year-class-specific linear discriminant function analysis yielded regional classification accuracies of 81% for 2012 and 85% for 2013, although samples were not obtained from all four regions in 2012. Combining year-classes resulted in an overall classification accuracy of 84%, thus demonstrating the usefulness of this approach. These results are encouraging yet highlight a need for more research to better evaluate the efficacy of vertebral chemistry to study elasmobranch population connectivity