Remembering the work of Phillip L. Geissler: A coda to his scientific trajectory

Phillip L. Geissler made important contributions to the statistical mechanics of biological polymers, heterogeneous materials, and chemical dynamics in aqueous environments. He devised analytical and computational methods that revealed the underlying organization of complex systems at the frontiers of biology, chemistry, and materials science. In this retrospective, we celebrate his work at these frontiers

Induction of humoral immune response to multiple recombinant Rhipicephalus appendiculatus antigens and their effect on tick feeding success and pathogen transmission

BACKGROUND: Rhipicephalus appendiculatus is the primary vector of Theileria parva, the etiological agent of East Coast fever (ECF), a devastating disease of cattle in sub-Saharan Africa. We hypothesized that a vaccine targeting tick proteins that are involved in attachment and feeding might affect feeding success and possibly reduce tick-borne transmission of T. parva. Here we report the evaluation of a multivalent vaccine cocktail of tick antigens for their ability to reduce R. appendiculatus feeding success and possibly reduce tick-transmission of T. parva in a natural host-tick-parasite challenge model. METHODS: Cattle were inoculated with a multivalent antigen cocktail containing recombinant tick protective antigen subolesin as well as two additional R. appendiculatus saliva antigens: the cement protein TRP64, and three different histamine binding proteins. The cocktail also contained the T. parva sporozoite antigen p67C. The effect of vaccination on the feeding success of nymphal and adult R. appendiculatus ticks was evaluated together with the effect on transmission of T. parva using a tick challenge model. RESULTS: To our knowledge, this is the first evaluation of the anti-tick effects of these antigens in the natural host-tick-parasite combination. In spite of evidence of strong immune responses to all of the antigens in the cocktail, vaccination with this combination of tick and parasite antigens did not appear to effect tick feeding success or reduce transmission of T. parva. CONCLUSION: The results of this study highlight the importance of early evaluation of anti-tick vaccine candidates in biologically relevant challenge systems using the natural tick-host-parasite combination

The Murchison Widefield Array

It is shown that the excellent Murchison Radio-astronomy Observatory site allows the Murchison Widefield Array to employ a simple RFI blanking scheme and still calibrate visibilities and form images in the FM radio band. The techniques described are running autonomously in our calibration and imaging software, which is currently being used to process an FM-band survey of the entire southern sky.Comment: Accepted for publication in Proceedings of Science [PoS(RFI2010)016]. 6 pages and 3 figures. Presented at RFI2010, the Third Workshop on RFI Mitigation in Radio Astronomy, 29-31 March 2010, Groningen, The Netherland

The yeast P5 type ATPase, Spf1, regulates manganese transport into the endoplasmic reticulum

The endoplasmic reticulum (ER) is a large, multifunctional and essential organelle. Despite intense research, the function of more than a third of ER proteins remains unknown even in the well-studied model organism Saccharomyces cerevisiae. One such protein is Spf1, which is a highly conserved, ER localized, putative P-type ATPase. Deletion of SPF1 causes a wide variety of phenotypes including severe ER stress suggesting that this protein is essential for the normal function of the ER. The closest homologue of Spf1 is the vacuolar P-type ATPase Ypk9 that influences Mn2+ homeostasis. However in vitro reconstitution assays with Spf1 have not yielded insight into its transport specificity. Here we took an in vivo approach to detect the direct and indirect effects of deleting SPF1. We found a specific reduction in the luminal concentration of Mn2+ in ∆spf1 cells and an increase following it’s overexpression. In agreement with the observed loss of luminal Mn2+ we could observe concurrent reduction in many Mn2+-related process in the ER lumen. Conversely, cytosolic Mn2+-dependent processes were increased. Together, these data support a role for Spf1p in Mn2+ transport in the cell. We also demonstrate that the human sequence homologue, ATP13A1, is a functionally conserved orthologue. Since ATP13A1 is highly expressed in developing neuronal tissues and in the brain, this should help in the study of Mn2+-dependent neurological disorders

An analysis of baseline data from the PROUD study: an open-label randomised trial of pre-exposure prophylaxis

Background: Pre-exposure prophylaxis (PrEP) has proven biological efficacy to reduce the sexual acquisition of the human immunodeficiency virus (HIV). The PROUD study found that PrEP conferred higher protection than in placebo-controlled trials, reducing HIV incidence by 86 % in a population with seven-fold higher HIV incidence than expected. We present the baseline characteristics of the PROUD study population and place the findings in the context of national sexual health clinic data. Methods: The PROUD study was designed to explore the real-world effectiveness of PrEP (tenofovir-emtricitabine) by randomising HIV-negative gay and other men who have sex with men (GMSM) to receive open-label PrEP immediately or after a deferral period of 12 months. At enrolment, participants self-completed two baseline questionnaires collecting information on demographics, sexual behaviour and lifestyle in the last 30 and 90 days. These data were compared to data from HIV-negative GMSM attending sexual health clinics in 2013, collated by Public Health England using the genitourinary medicine clinic activity database (GUMCAD). Results: The median age of participants was 35 (IQR: 29–43). Typically participants were white (81 %), educated at a university level (61 %) and in full-time employment (72 %). Of all participants, 217 (40 %) were born outside the UK. A sexually transmitted infection (STI) was reported to have been diagnosed in the previous 12 months in 330/515 (64 %) and 473/544 (87 %) participants reported ever having being diagnosed with an STI. At enrolment, 47/280 (17 %) participants were diagnosed with an STI. Participants reported a median (IQR) of 10 (5–20) partners in the last 90 days, a median (IQR) of 2 (1–5) were condomless sex acts where the participant was receptive and 2 (1–6) were condomless where the participant was insertive. Post-exposure prophylaxis had been prescribed to 184 (34 %) participants in the past 12 months. The number of STI diagnoses was high compared to those reported in GUMCAD attendees. Conclusions: The PROUD study population are at substantially higher risk of acquiring HIV infection sexually than the overall population of GMSM attending sexual health clinics in England. These findings contribute to explaining the extraordinary HIV incidence rate during follow-up and demonstrate that, despite broad eligibility criteria, the population interested in PrEP was highly selective. Trial registration: Current Controlled TrialsISRCTN94465371. Date of registration: 28 February 2013

Simultaneous observations of giant pulses from the Crab pulsar, with the Murchison Widefield Array and Parkes radio telescope: implications for the giant pulse emission mechanism

We report on observations of giant pulses from the Crab pulsar performed simultaneously with the Parkes radio telescope and the incoherent combination of the Murchison Widefield Array (MWA) antenna tiles. The observations were performed over a duration of approximately one hour at a center frequency of 1382 MHz with 340 MHz bandwidth at Parkes, and at a center frequency of 193 MHz with 15 MHz bandwidth at the MWA. Our analysis has led to the detection of 55 giant pulses at the MWA and 2075 at Parkes above a threshold of 3.5σ and 6.5σ, respectively. We detected 51% of the MWA giant pulses at the Parkes radio telescope, with spectral indices in the range of-3.6 > α > -4.9 (Sv μ ∝ Va). We present a Monte Carlo analysis supporting the conjecture that the giant pulse emission in the Crab is intrinsically broadband, the less than 100% correlation being due to the relative sensitivities of the two instruments and the width of the spectral index distribution. Our observations are consistent with the hypothesis that the spectral index of giant pulses is drawn from normal distribution of standard deviation 0.6, but with a mean that displays an evolution with frequency from −3.00 at 1382 MHz, to −2.85 at 192 MHz

Simultaneous observations of giant pulses from the Crab pulsar, with the Murchison Widefield Array and Parkes radio telescope: implications for the giant pulse emission mechanism

We report on observations of giant pulses from the Crab pulsar performed simultaneously with the Parkes radio telescope and the incoherent combination of the Murchison Widefield Array (MWA) antenna tiles. The observations were performed over a duration of approximately one hour at a center frequency of 1382 MHz with 340 MHz bandwidth at Parkes, and at a center frequency of 193 MHz with 15 MHz bandwidth at the MWA. Our analysis has led to the detection of 55 giant pulses at the MWA and 2075 at Parkes above a threshold of 3.5σ and 6.5σ, respectively. We detected 51% of the MWA giant pulses at the Parkes radio telescope, with spectral indices in the range of-3.6 > α > -4.9 (Sv μ ∝ Va). We present a Monte Carlo analysis supporting the conjecture that the giant pulse emission in the Crab is intrinsically broadband, the less than 100% correlation being due to the relative sensitivities of the two instruments and the width of the spectral index distribution. Our observations are consistent with the hypothesis that the spectral index of giant pulses is drawn from normal distribution of standard deviation 0.6, but with a mean that displays an evolution with frequency from −3.00 at 1382 MHz, to −2.85 at 192 MHz

Dynamics on the double morse potential: a paradigm for roaming reactions with no saddle points

In this paper we analyze a two-degree-of-freedom Hamiltonian system constructed from two planar Morse potentials. The resulting potential energy surface has two potential wells surrounded by an unbounded flat region containing no critical points. In addition, the model has an index one saddle between the potential wells. We study the dynamical mechanisms underlying transport between the two potential wells, with emphasis on the role of the flat region surrounding the wells. The model allows us to probe many of the features of the “roaming mechanism” whose reaction dynamics are of current interest in the chemistry community