Ordinary Share Price Behaviour Around 'C' Share Issues by Investment Trusts

This paper examines the "C" share issue, a method of issuing shares which is peculiar to the UK investment trust industry. In particular, we analyse abnormal returns and discount/premium to net asset value behaviour of the ordinary shares both before and after the announcement of "C" share issues. The research was conducted using event study methodology and an innovative approach to the analysis of discount/premium movements. The results suggest a tendency for the ordinary shares to outperform the FT-SE Actuaries Investment Trust Index over the six months following a "C" share issue announcement, despite a reduction in the premium to net asset value rating of the shares over the same period

T‐cell pseudolymphoma secondary to ixazomib for multiple myeloma

We present a case of a 54-year-old male with multiple myeloma (MM) who presented with widespread pruritic erythematous lesions following ixazomib treatment. This occurred after his third cycle of treatment with ixazomib, thalidomide and dexamethasone and was controlled by potent steroids and temporary cessation of ixazomib. The strong correlation between the timeline of the rash, ixazomib treatment and subsequent cessation led to a diagnosis of a drug-induced rash. Skin biopsy histology, immunochemistry and the absence of monoclonal T-cell receptor gene rearrangement further confirmed the diagnosis of a T-cell pseudolymphoma secondary to ixazomib. Ixazomib is an oral proteasome inhibitor used in the treatment of MM. Other proteasome inhibitors have been reported to trigger cutaneous adverse effects. However, to our knowledge, this is the first report of pseudolymphoma following proteasome inhibitor use. Dermatologists should be aware of this potential effect and the possible management pathways such as cessation and dose reduction

Global sexual fertility in the opportunistic pathogen aspergillus fumigatus and identification of new supermater strains

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. A sexual cycle in Aspergillus fumigatus was first described in 2009 with isolates from Dublin, Ireland. However, the extent to which worldwide isolates can undergo sexual reproduction has remained unclear. In this study a global collection of 131 isolates was established with a near 1:1 ratio of mating types. All isolates were crossed to MAT1-1 or MAT1-2 Irish strains, and a subset of isolates from different continents were crossed together. Ninety seven percent of isolates were found to produce cleistothecia with at least one mating partner, showing that sexual fertility is not limited to the Irish population but is a characteristic of global A. fumigatus. However, large variation was seen in numbers of cleistothecia produced per cross, suggesting differences in the possibility for genetic exchange between strains in nature. The majority of crosses produced ascospores with >50% germination rates, but with wide variation evident. A high temperature heat shock was required to induce ascospore germination. Finally, a new set of highly fertile MAT1-1 and MAT1-2 supermater strains were identified and pyrimidine auxotrophs generated for community use. Results provide insights into the potential for the A. fumigatus sexual cycle to generate genetic variation and allow gene flow of medically important traits

Do You See What I Mean? Corticospinal Excitability During Observation of Culture-Specific Gestures

People all over the world use their hands to communicate expressively. Autonomous gestures, also known as emblems, are highly social in nature, and convey conventionalized meaning without accompanying speech. To study the neural bases of cross-cultural social communication, we used single pulse transcranial magnetic stimulation (TMS) to measure corticospinal excitability (CSE) during observation of culture-specific emblems. Foreign Nicaraguan and familiar American emblems as well as meaningless control gestures were performed by both a Euro-American and a Nicaraguan actor. Euro-American participants demonstrated higher CSE during observation of the American compared to the Nicaraguan actor. This motor resonance phenomenon may reflect ethnic and cultural ingroup familiarity effects. However, participants also demonstrated a nearly significant (p = 0.053) actor by emblem interaction whereby both Nicaraguan and American emblems performed by the American actor elicited similar CSE, whereas Nicaraguan emblems performed by the Nicaraguan actor yielded higher CSE than American emblems. The latter result cannot be interpreted simply as an effect of ethnic ingroup familiarity. Thus, a likely explanation of these findings is that motor resonance is modulated by interacting biological and cultural factors

Shotgun Lipidomic Profiling of the NCI60 Cell Line Panel Using Rapid Evaporative Ionization Mass Spectrometry

Rapid evaporative ionization mass spectrometry (REIMS) was used for the rapid mass spectrometric profiling of cancer cell lines. Spectral reproducibility was assessed for three different cell lines, and the extent of interclass differences and intraclass variance was found to allow the identification of these cell lines based on the REIMS data. Subsequently, the NCI60 cell line panel was subjected to REIMS analysis, and the resulting data set was investigated for its distinction of individual cell lines and different tissue types of origin. Information content of REIMS spectral profiles of cell lines were found to be similar to those obtained from mammalian tissues although pronounced differences in relative lipid intensity were observed. Ultimately, REIMS was shown to detect changes in lipid content of cell lines due to mycoplasma infection. The data show that REIMS is an attractive means to study cell lines involving minimal sample preparation and analysis times in the range of seconds. © 2016 American Chemical Society

MUSE-ALMA Halos XI: Gas flows in the circumgalactic medium

The flow of gas into and out of galaxies leaves traces in the circumgalactic medium which can then be studied using absorption lines towards background quasars. We analyse 27 log(N_HI) > 18.0 HI absorbers at z = 0.2 to 1.4 from the MUSE-ALMA Halos survey with at least one galaxy counterpart within a line of sight velocity of +/-500 km s^{-1}. We perform 3D kinematic forward modelling of these associated galaxies to examine the flow of dense, neutral gas in the circumgalactic medium. From the VLT/MUSE, HST broadband imaging and VLT/UVES and Keck/HIRES high-resolution UV quasar spectroscopy observations, we compare the impact parameters, star-formation rates and stellar masses of the associated galaxies with the absorber properties. We find marginal evidence for a bimodal distribution in azimuthal angles for strong HI absorbers, similar to previous studies of the MgII and OVI absorption lines. There is no clear metallicity dependence on azimuthal angle and we suggest a larger sample of absorbers are required to fully test the relationship predicted by cosmological hydrodynamical simulations. A case-by-case study of the absorbers reveals that ten per cent of absorbers are consistent with gas accretion, up to 30 per cent trace outflows while the remainder trace gas in the galaxy disk, the intragroup medium and low-mass galaxies below the MUSE detection limit. Our results highlight that the baryon cycle directly affects the dense neutral gas required for star-formation and plays a critical role in galaxy evolution.Comment: 13 pages, 6 figures, 12 pages of appendix. Accepted for publication in MNRA

NSC23925, Identified in a High-Throughput Cell-Based Screen, Reverses Multidrug Resistance

Multidrug resistance (MDR) is a major factor which contributes to the failure of cancer chemotherapy, and numerous efforts have been attempted to overcome MDR. To date, none of these attempts have yielded a tolerable and effective therapy to reverse MDR; thus, identification of new agents would be useful both clinically and scientifically.To identify small molecule compounds that can reverse chemoresistance, we developed a 96-well plate high-throughput cell-based screening assay in a paclitaxel resistant ovarian cancer cell line. Coincubating cells with a sublethal concentration of paclitaxel in combination with each of 2,000 small molecule compounds from the National Cancer Institute Diversity Set Library, we identified a previously uncharacterized molecule, NSC23925, that inhibits Pgp1 and reverses MDR1 (Pgp1) but does not inhibit MRP or BCRP-mediated MDR. The cytotoxic activity of NSC23925 was further evaluated using a panel of cancer cell lines expressing Pgp1, MRP, and BCRP. We found that at a concentration of >10 microM NSC23925 moderately inhibits the proliferation of both sensitive and resistant cell lines with almost equal activity, but its inhibitory effect was not altered by co-incubation with the Pgp1 inhibitor, verapamil, suggesting that NSC23925 itself is not a substrate of Pgp1. Additionally, NSC23925 increases the intracellular accumulation of Pgp1 substrates: calcein AM, Rhodamine-123, paclitaxel, mitoxantrone, and doxorubicin. Interestingly, we further observed that, although NSC23925 directly inhibits the function of Pgp1 in a dose-dependent manner without altering the total expression level of Pgp1, NSC23925 actually stimulates ATPase activity of Pgp, a phenomenon seen in other Pgp inhibitors.The ability of NSC23925 to restore sensitivity to the cytotoxic effects of chemotherapy or to prevent resistance could significantly benefit cancer patients

Shifting the Paradigm: The Putative Mitochondrial Protein ABCB6 Resides in the Lysosomes of Cells and in the Plasma Membrane of Erythrocytes

ABCB6, a member of the adenosine triphosphate–binding cassette (ABC) transporter family, has been proposed to be responsible for the mitochondrial uptake of porphyrins. Here we show that ABCB6 is a glycoprotein present in the membrane of mature erythrocytes and in exosomes released from reticulocytes during the final steps of erythroid maturation. Consistent with its presence in exosomes, endogenous ABCB6 is localized to the endo/lysosomal compartment, and is absent from the mitochondria of cells. Knock-down studies demonstrate that ABCB6 function is not required for de novo heme biosynthesis in differentiating K562 cells, excluding this ABC transporter as a key regulator of porphyrin synthesis. We confirm the mitochondrial localization of ABCB7, ABCB8 and ABCB10, suggesting that only three ABC transporters should be classified as mitochondrial proteins. Taken together, our results challenge the current paradigm linking the expression and function of ABCB6 to mitochondria