1,028 research outputs found
Dynamic performance of squeeze-film bearings
Earlier work has shown that oil-film forces can be modelled by linear coefficients. Identification techniques were used to generate numerical values for these coefficients. This paper has shown the invalidity of applying the perturbation techniques normally used in bearing studies to derive expressions for linearized coefficients to represent a cavitated oil-film. An alternative approach was developed based upon energy techniques to obtain estimates for linearized coefficients. Some current work being undertaken suggests that an alternative analytical approach is possible. These results will be reported in due course
Reducing ambulance on-scene times for suspected stroke through an evidence-based training package: an interim analysis
Culture-adapted Plasmodium falciparum isolates from UK travellers: in vitro drug sensitivity, clonality and drug resistance markers.
BACKGROUND: The screening of lead compounds against in vitro parasite cultures is an essential step in the development of novel anti-malarial drugs, but currently relies on laboratory parasite lines established in vitro during the last century. This study sought to establish in continuous culture a series of recent Plasmodium falciparum isolates to represent the current parasite populations in Africa, all of which are now exposed to artemisinin combination therapy. METHODS: Pre-treatment P. falciparum isolates were obtained in EDTA, and placed into continuous culture after sampling of DNA. One post-treatment blood sample was also collected for each donor to monitor parasite clonality during clearance in vivo. IC₅₀ estimates were obtained for 11 anti-malarial compounds for each established parasite line, clonal multiplicity measured in vivo and in vitro, and polymorphic sites implicated in parasite sensitivity to drugs were investigated at the pfmdr1, pfcrt, pfdhfr, pfdhps and pfap2mu loci before and after treatment, and in the cultured lines. RESULTS: Plasmodium falciparum isolates from seven malaria patients with recent travel to three West African and two East African countries were successfully established in long-term culture. One of these, HL1211, was from a patient with recrudescent parasitaemia 14 days after a full course of artemether-lumefantrine. All established culture lines were shown to be polyclonal, reflecting the in vivo isolates from which they were derived, and at least two lines reliably produce gametocytes in vitro. Two lines displayed high chloroquine IC₅₀ estimates, and carried the CVIET haplotype at codons 72-76, whereas the remaining five lines carried the CVMNK haplotype and were sensitive in vitro. All were sensitive to the endoperoxides dihydroartemisinin and OZ277, but IC₅₀ estimates for lumefantrine varied, with the least sensitive parasites carrying pfmdr1 alleles encoding Asn at codon 86. CONCLUSIONS: This study describes the establishment in continuous culture, in vitro drug sensitivity testing and molecular characterization of a series of multiclonal P. falciparum isolates taken directly from UK malaria patients following recent travel to various malaria-endemic countries in Africa. These "HL" isolates are available as an open resource for studies of drug response, antigenic diversity and other aspects of parasite biology
Herpes simplex virus as a model vector system for gene therapy in renal disease
Herpes simplex virus as a model vector system for gene therapy in renal disease. The past decade has been marked by significant advances in the application of gene transfer into living cells of animals and humans. These approaches have been tested in a few animal models of inherited and acquired renal diseases, including carbonic anhydrase II deficiency 1 and experimental glomerulonephritis2,3. Gene transfer into proximal tubular cells has been successfully accomplished by intrarenal arterial infusion of a liposomal complex4 or an adenoviral vector5. Tubular cells from the papilla and medulla have been selectively transduced by retrograde infusion into the pelvi-calyceal system of an adenoviral vector containing a reporter for β-galactosidase5. Although the results of these initial studies are promising, further studies to optimize viral vectors, maximize gene delivery, minimize side-effects, and develop cell-specific and long-term regulated gene expression are critical to the success of gene therapy targeted to specific compartments of the kidney. Our recent efforts have focused on defining the cellular pathways responsible for viral entry and infection into renal epithelial cells using herpes simplex virus (HSV) as a model vector. We anticipate that a solid understanding of the basic scientific principles underlying viral entry and gene expression into specific populations of renal cells will facilitate the design of successful therapeutic viral-based gene transfer strategies
Over half of breakpoints in gene pairs involved in cancer-specific recurrent translocations are mapped to human chromosomal fragile sites.
Gene rearrangements such as chromosomal translocations have been shown to
contribute to cancer development. Human chromosomal fragile sites are regions of the genome
especially prone to breakage, and have been implicated in various chromosome abnormalities found
in cancer. However, there has been no comprehensive and quantitative examination of the location
of fragile sites in relation to all chromosomal aberrations
Acanthodians from the Silurian–Devonian boundary beds of Novaya Zemlya Archipelago, Russia
© 2018, © 2018 Geologiska Föreningen. An acanthodian assemblage is reported for the first time from the Silurian–Devonian boundary beds of Novaya Zemlya Archipelago, Russia. The acanthodian scales and rare other vertebrate microremains were in a sample collected from the Reliktovoe Formation of the western coast of Inostantzev Bay, North Island. The assemblage includes Gomphonchus mediocostatus, Gomphonchoporus hoppei taxa previously described from the Pridoli–Lochkovian of Laurussia, and Taimyrolepis composita occurred in the Lochkovian of Siberia. Gomphonchus mediocostatus and Gomphonchoporus hoppei are widely distributed in the Baltica palaeogeographic province, and Taimyrolepis is known from the Siberia province, indicating connection between those provinces
New Information on Culmacanthus (Acanthodii: Diplacanthiformes) from the ?Early–Middle Devonian of Southeastern Australia
A new articulated acanthodian from the Devonian Bunga Beds on the south coast of New South Wales is assigned to Culmacanthus sp., and reveals that this diplacanthiform has smooth dental plates on the occlusal surfaces of the lower jaws. Within the Acanthodii, this type of element was first identified in “Gladiobranchus” probaton from the earliest Devonian MOTH locality, Northwest Territories, Canada, and has now also been identified in “Euthacanthus” curtus (Lochkovian, Lower Old Red Sandstone, Scotland) and Diplacanthus spp. (Givetian, Scotland and Frasnian, Canada). The dental plates in Culmacanthus have the same morphology as those of “Gladiobranchus” probaton and “Euthacanthus” curtus. Reexamination of type specimens of Culmacanthus shows that its pectoral fin spines do not have long insertions, and the purported lack of prepectoral, admedian and prepelvic fin spines could be due to loss of the elements before burial rather than morphological absence
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