Thermodynamical Properties of a Rotating Ideal Bose Gas

In a recent experiment, a Bose-Einstein condensate was trapped in an anharmonic potential which is well approximated by a harmonic and a quartic part. The condensate was set into such a fast rotation that the centrifugal force in the corotating frame overcompensates the harmonic part in the plane perpendicular to the rotation axis. Thus, the resulting trap potential became Mexican-hat shaped. We present an analysis for an ideal Bose gas which is confined in such an anharmonic rotating trap within a semiclassical approximation where we calculate the critical temperature, the condensate fraction, and the heat capacity. In particular, we examine in detail how these thermodynamical quantities depend on the rotation frequency.Comment: Author Information under http://www.theo-phys.uni-essen.de/tp/ags/pelster_dir

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

Verapamil-Sensitive Transport of Quinacrine and Methylene Blue via the Plasmodium falciparum Chloroquine Resistance Transporter Reduces the Parasite's Susceptibility to these Tricyclic Drugs.

BACKGROUND: It is becoming increasingly apparent that certain mutations in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) alter the parasite's susceptibility to diverse compounds. Here we investigated the interaction of PfCRT with 3 tricyclic compounds that have been used to treat malaria (quinacrine [QC] and methylene blue [MB]) or to study P. falciparum (acridine orange [AO]). METHODS: We measured the antiplasmodial activities of QC, MB, and AO against chloroquine-resistant and chloroquine-sensitive P. falciparum and determined whether QC and AO affect the accumulation and activity of chloroquine in these parasites. We also assessed the ability of mutant (PfCRT(Dd2)) and wild-type (PfCRT(D10)) variants of the protein to transport QC, MB, and AO when expressed at the surface of Xenopus laevis oocytes. RESULTS: Chloroquine resistance-conferring isoforms of PfCRT reduced the susceptibility of the parasite to QC, MB, and AO. In chloroquine-resistant (but not chloroquine-sensitive) parasites, AO and QC increased the parasite's accumulation of, and susceptibility to, chloroquine. All 3 compounds were shown to bind to PfCRT(Dd2), and the transport of QC and MB via this protein was saturable and inhibited by the chloroquine resistance-reverser verapamil. CONCLUSIONS: Our findings reveal that the PfCRT(Dd2)-mediated transport of tricyclic antimalarials reduces the parasite's susceptibility to these drugs

Phase transition from straight into twisted vortex-lines in dipolar Bose-Einstein condensates

The non-local non-linearity introduced by the dipole-dipole interaction plays a crucial role in the physics of dipolar Bose-Einstein condensates. In particular, it may distort significantly the stability of straight vortex lines due to the rotonization of the Kelvin-wave spectrum. In this paper we analyze this instability showing that it leads to a second-order-like phase transition from a straight vortex-line into novel helical or snake-like configurations, depending on the dipole orientation.Comment: 11 pages, 6 figures, Accepted for publication in New J. Phy

The value of competitive employment:In-depth accounts of people with intellectual disabilities

BackgroundIncreasing the societal participation of people with intellectual disabilities via competitive employment requires a full understanding of what this means to them. This paper aims to provide an in‐depth examination of the lived experiences of people with intellectual disabilities in competitive employment.MethodInterviews were conducted with six participants with mild intellectual disability or borderline functioning and good verbal communication skills. Interviews were analysed according to the guidelines of interpretative phenomenological analysis (IPA). Member checks were conducted.ResultsAnalysis yielded three main themes: (a) Building on my life experiences, (b) My place at work and (c) Being a valuable member of society, like everyone else.ConclusionsCompetitive employment could make a substantial contribution to the sense of belonging to society and quality of life of people with intellectual disabilities. Nevertheless, they must cope with stigma‐related obstacles and feelings of being dependent on others in the work environment

Observation of vortex formation in an oscillating trapped Bose-Einstein condensate

We report on the observation of vortex formation in a Bose-Einstein condensate of Rb-87 atoms. Vortices are generated by superimposing an oscillating excitation to the trapping potential introduced by an external magnetic field. For small amplitudes of the external excitation field we observe a bending of the cloud axis. Increasing the amplitude we observe formation of a growing number of vortices in the sample. Shot-to-shot variations in both vortex number and position within the condensed cloud are observed, probably due to the intrinsic vortex nucleation dynamics. We discuss the possible formation of vortices and anti-vortices in the sample as well as possible mechanisms for vortex nucleation.Comment: 1 figure added, text modified, accepted for publication Phys. Rev.

pfk13-Independent Treatment Failure in Four Imported Cases of Plasmodium falciparum Malaria Treated with Artemether-Lumefantrine in the United Kingdom.

We present case histories of four patients treated with artemether-lumefantrine for falciparum malaria in UK hospitals in 2015 to 2016. Each subsequently presented with recurrent symptoms and Plasmodium falciparum parasitemia within 6 weeks of treatment with no intervening travel to countries where malaria is endemic. Parasite isolates, all of African origin, harbored variants at some candidate resistance loci. No evidence of pfk13-mediated artemisinin resistance was found. Vigilance for signs of unsatisfactory antimalarial efficacy among imported cases of malaria is recommended

Exploiting retrograde transport of Shiga-like toxin 1 for the delivery of exogenous antigens into the MHC class I presentation pathway

AbstractShiga-like toxin 1 (SLT) from Escherichia coli 0157:H7 enters mammalian cells by endocytosis from the cell surface to the endoplasmic reticulum before translocating into the cytosol. Here, SLT was engineered at its N- or C-terminus to carry a peptide derived from influenza virus Matrix protein for delivery to major histocompatibility complex (MHC) class I molecules. We show that SLT N-Ma was capable of sensitising cells for lysis by appropriate cytotoxic T-lymphocytes whilst no killing of SLT-resistant cells was observed. Our results demonstrate that peptide was liberated intracellularly and that retrograde transport of a disarmed cytotoxic protein can intersect the MHC class 1 presentation pathway

The physics of dipolar bosonic quantum gases

This article reviews the recent theoretical and experimental advances in the study of ultracold gases made of bosonic particles interacting via the long-range, anisotropic dipole-dipole interaction, in addition to the short-range and isotropic contact interaction usually at work in ultracold gases. The specific properties emerging from the dipolar interaction are emphasized, from the mean-field regime valid for dilute Bose-Einstein condensates, to the strongly correlated regimes reached for dipolar bosons in optical lattices.Comment: Review article, 71 pages, 35 figures, 350 references. Submitted to Reports on Progress in Physic

Plasmodium knowlesi exhibits distinct in vitro drug susceptibility profiles from those of Plasmodium falciparum.

New antimalarial agents are identified and developed after extensive testing on Plasmodium falciparum parasites that can be grown in vitro. These susceptibility studies are important to inform lead optimisation and support further drug development. Until recently, little was known about the susceptibility of non-falciparum species as these had not been adapted to in vitro culture. The recent culture adaptation of P. knowlesi has therefore offered an opportunity to routinely define the drug susceptibility of this species, which is phylogenetically closer to all other human malarias than is P. falciparum. We compared the in vitro susceptibility of P. knowlesi and P. falciparum to a range of established and novel antimalarial agents under identical assay conditions. We demonstrated that P. knowlesi is significantly less susceptible than P. falciparum to six of the compounds tested; and notably these include three ATP4 inhibitors currently under development as novel antimalarial agents, and one investigational antimalarial, AN13762, which is 67 fold less effective against P. knowlesi. For the other compounds there was a less than two-fold difference in susceptibility between species. We then compared the susceptibility of a recent P. knowlesi isolate, UM01, to that of the well-established, older A1-H.1 clone. This recent isolate showed similar in vitro drug susceptibility to the A1-H.1 clone, supporting the ongoing use of the better characterised clone to further study drug susceptibility. Lastly, we used isobologram analysis to explore the interaction of a selection of drug combinations and showed similar drug interactions across species. The species differences in drug susceptibility reported by us here and previously, support adding in vitro drug screens against P. knowlesi to those using P. falciparum strains to inform new drug discovery and lead optimisation