Cancer immunology and canine malignant melanoma: a comparative review

Oral canine malignant melanoma (CMM) is a spontaneously occurring aggressive tumour with relatively few medical treatment options, which provides a suitable model for the disease in humans. Historically, multiple immunotherapeutic strategies aimed at provoking both innate and adaptive anti-tumour immune responses have been published with varying levels of activity against CMM. Recently, a plasmid DNA vaccine expressing human tyrosinase has been licensed for the adjunct treatment of oral CMM. This article reviews the immunological similarities between CMM and the human counterpart; mechanisms by which tumours evade the immune system; reasons why melanoma is an attractive target for immunotherapy; the premise of whole cell, dendritic cell (DC), viral and DNA vaccination strategies alongside preliminary clinical results in dogs. Current “gold standard” treatments for advanced human malignant melanoma are evolving quickly with remarkable results being achieved following the introduction of immune checkpoint blockade and adoptively transferred cell therapies. The rapidly expanding field of cancer immunology and immunotherapeutics means that rational targeting of this disease in both species should enhance treatment outcomes in veterinary and human clinics

How water flow, geometry and material properties drive plant movements

Plants are dynamic. They adjust their shape for feeding, defence and reproduction. Such plant movements are critical for their survival. We present selected examples covering a range of movements from single cell to tissue level and over a range of timescales. We focus on reversible turgor-driven shape changes. Recent insights into the mechanisms of stomata, bladderwort, the waterwheel and the Venus flytrap are presented. The underlying physical principles (turgor, osmosis, membrane permeability, wall stress, snap buckling, elastic instability) are highlighted and advances in our understanding of these processes are summarised

Destabilization of α-helical structure in solution improves bactericidal activity of antimicrobial peptides: Opposing effects on bacterial and viral targets

We have previously examined the mechanism of antimicrobial peptides on the outer membrane of vaccinia virus. Here we show that the formulation of peptides LL37 and magainin-2B amide in polysorbate 20 (Tween-20™) results in greater reductions in virus titre than formulation without detergent, and the effect is replicated by substitution of polysorbate 20 with high ionic strength buffer. In contrast, formulation with polysorbate 20 or high ionic strength buffer has the opposite effect on bactericidal activity of both peptides, resulting in lesser reductions in titre for both gram-positive and gram-negative bacteria. Circular dichroism spectroscopy shows that the differential action of polysorbate 20 and salt on the virucidal and bactericidal activities correlates with the α-helical content of peptide secondary structure in solution, suggesting that the virucidal and bactericidal activities are mediated through distinct mechanisms. The correlation of a defined structural feature with differential activity against a host-derived viral membrane and the membranes of both gram-positive and gram-negative bacteria suggests that overall helical content in solution under physiological conditions is an important feature for consideration in the design and development of candidate peptide-based antimicrobial compounds

Intra-day Variability of Sagittarius A* at 3 Millimeters

We report observations and analysis of flux monitoring of Sagittarius A* at 3-mm wavelength using the OVRO millimeter interferometer over a period of eight days (2002 May 23-30). Frequent phase and flux referencing (every 5 minutes) with the nearby calibrator source J1744-312 was employed to control for instrumental and atmospheric effects. Time variations are sought by computing and subtracting, from each visibility in the database, an average visibility obtained from all the data acquired in our monitoring program having similar uv spacings. This removes the confusing effects of baseline-dependent, correlated flux interference caused by the static, thermal emission from the extended source Sgr A West. Few-day variations up to ~20% and intra-day variability of \~20% and in some cases up to ~40% on few-hour time scales emerge from the differenced data on SgrA*. Power spectra of the residuals indicate the presence of hourly variations on all but two of the eight days. Monte Carlo simulation of red-noise light curves indicates that the hourly variations are well described by a red-noise power spectrum with P(f) ~ f^(-1). Of particular interest is a ~2.5 hour variation seen prominently on two consecutive days. An average power spectrum from all eight days of data reveals noteworthy power on this time scale. There is some indication that few-hour variations are more pronounced on days when the average daily flux is highest. We briefly discuss the possibility that these few-hour variations are due to the dynamical modulation of accreting gas around the central supermassive black hole, as well as the implications for the structure of the SgrA* photosphere at 3 mm. Finally, these data have enabled us to produce a high sensitivity 3-mm map of the extended thermal emission surrounding SgrA*.Comment: Accepted for publication in The Astrophysical Journal Letters, 8 pages, 4 figure

Ordinal Probit Functional Regression Models with Application to Computer-Use Behavior in Rhesus Monkeys

Research in functional regression has made great strides in expanding to non-Gaussian functional outcomes, however the exploration of ordinal functional outcomes remains limited. Motivated by a study of computer-use behavior in rhesus macaques (\emph{Macaca mulatta}), we introduce the Ordinal Probit Functional Regression Model or OPFRM to perform ordinal function-on-scalar regression. The OPFRM is flexibly formulated to allow for the choice of different basis functions including penalized B-splines, wavelets, and O'Sullivan splines. We demonstrate the operating characteristics of the model in simulation using a variety of underlying covariance patterns showing the model performs reasonably well in estimation under multiple basis functions. We also present and compare two approaches for conducting posterior inference showing that joint credible intervals tend to out perform point-wise credible. Finally, in application, we determine demographic factors associated with the monkeys' computer use over the course of a year and provide a brief analysis of the findings

A Spitzer Study of the Mass Loss Histories of Three Bipolar Pre-Planetary Nebulae

We present the results of far-infrared imaging of extended regions around three bipolar pre-planetary nebulae, AFGL 2688, OH 231.8+4.2, and IRAS 16342$-$3814, at 70 and 160 $\mu$m with the MIPS instrument on the Spitzer Space Telescope. After a careful subtraction of the point spread function of the central star from these images, we place constraints on the existence of extended shells and thus on the mass outflow rates as a function of radial distance from these stars. We find no apparent extended emission in AFGL 2688 and OH 231.8+4.2 beyond 100 arcseconds from the central source. In the case of AFGL 2688, this result is inconsistent with a previous report of two extended dust shells made on the basis of ISO observations. We derive an upper limit of $2.1\times10^{-7}$ M$_\odot$ yr$^{-1}$ and $1.0\times10^{-7}$ M$_\odot$ yr$^{-1}$ for the dust mass loss rate of AFGL 2688 and OH 231.8, respectively, at 200 arcseconds from each source. In contrast to these two sources, IRAS 16342$-$3814 does show extended emission at both wavelengths, which can be interpreted as a very large dust shell with a radius of $\sim$ 400 arcseconds and a thickness of $\sim$ 100 arcseconds, corresponding to 4 pc and 1 pc, respectively, at a distance of 2 kpc. However, this enhanced emission may also be galactic cirrus; better azimuthal coverage is necessary for confirmation of a shell. If the extended emission is a shell, it can be modeled as enhanced mass outflow at a dust mass outflow rate of $1.5\times10^{-6}$ M$_\odot$ yr$^{-1}$ superimposed on a steady outflow with a dust mass outflow rate of $1.5\times10^{-7}$ M$_\odot$ yr$^{-1}$. It is likely that this shell has swept up a substantial mass of interstellar gas during its expansion, so these estimates are upper limits to the stellar mass loss rate.Comment: 31 pages, 12 figures, accepted to A