Effect of dietary omega-3 fatty acids on castrate-resistant prostate cancer and tumor-associated macrophages.

BackgroundM2-like macrophages are associated with the pathogenesis of castrate-resistant prostate cancer (CRPC). We sought to determine if dietary omega-3 fatty acids (ω-3 FAs) delay the development and progression of CRPC and inhibit tumor-associated M2-like macrophages.MethodsMycCap cells were grown subcutaneously in immunocompetent FVB mice. Mice were castrated when tumors reached 300 mm2. To study effects of dietary ω-3 FAs on development of CRPC, ω-3 or ω-6 diets were started 2 days after castration and mice sacrificed after early regrowth of tumors. To study ω-3 FA effects on progression of CRPC, tumors were allowed to regrow after castration before starting the diets. M2 (CD206+) macrophages were isolated from allografts to examine ω-3 FA effects on macrophage function. Omega-3 fatty acid effects on androgen-deprived RAW264.7 M2 macrophages were studied by RT-qPCR and a migration/ invasion assay.ResultsThe ω-3 diet combined with castration lead to greater MycCap tumor regression (tumor volume reduction: 182.2 ± 33.6 mm3) than the ω-6 diet (tumor volume reduction: 148.3 ± 35.2; p = 0.003) and significantly delayed the time to CRPC (p = 0.006). Likewise, the ω-3 diet significantly delayed progression of established castrate-resistant MycCaP tumors (p = 0.003). The ω-3 diet (as compared to the ω-6 diet) significantly reduced tumor-associated M2-like macrophage expression of CSF-1R in the CRPC development model, and matrix metallopeptidase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in the CRPC progression model. Migration of androgen-depleted RAW264.7 M2 macrophages towards MycCaP cells was reversed by addition of docosahexaenoic acid (ω-3).ConclusionsDietary omega-3 FAs (as compared to omega-6 FAs) decreased the development and progression of CRPC in an immunocompetent mouse model, and had inhibitory effects on M2-like macrophage function. Clinical trials are warranted evaluating if a fish oil-based diet can delay the time to castration resistance in men on androgen deprivation therapy, whereas further preclinical studies are warranted evaluating fish oil for more advanced CRPC

A Spitzer Space Telescope far-infrared spectral atlas of compact sources in the Magellanic Clouds. II. The Small Magellanic Cloud

We present 52-93 micron spectra, obtained with the Spitzer Space Telescope, of luminous compact far-IR sources in the SMC. These comprise 9 Young Stellar Objects (YSOs), the compact HII region N81 and a similar object within N84, and two red supergiants (RSGs). The spectra of the sources in N81 (of which we also show the ISO-LWS spectrum between 50-170 micron) and N84 both display strong [OI] 63-micron and [OIII] 88-micron fine-structure line emission. We attribute these lines to strong shocks and photo-ionized gas, respectively, in a ``champagne flow'' scenario. The nitrogen content of these two HII regions is very low, definitely N/O<0.04 but possibly as low as N/O<0.01. Overall, the oxygen lines and dust continuum are weaker in star-forming objects in the SMC than in the LMC. We attribute this to the lower metallicity of the SMC compared to that of the LMC. Whilst the dust mass differs in proportion to metallicity, the oxygen mass differs less; both observations can be reconciled with higher densities inside star-forming cloud cores in the SMC than in the LMC. The dust in the YSOs in the SMC is warmer (37-51 K) than in comparable objects in the LMC (32-44 K). We attribute this to the reduced shielding and reduced cooling at the low metallicity of the SMC. On the other hand, the efficiency of the photo-electric effect to heat the gas is found to be indistinguishable to that measured in the same manner in the LMC, 0.1-0.3%. This may result from higher cloud-core densities, or smaller grains, in the SMC. The dust associated with the two RSGs in our SMC sample is cool, and we argue that it is swept-up interstellar dust, or formed (or grew) within the bow-shock, rather than dust produced in these metal-poor RSGs themselves. Strong emission from crystalline water ice is detected in at least one YSO. (abridged)Comment: Accepted for publication in The Astronomical Journa

Computer simulation of syringomyelia in dogs

Syringomyelia is a pathological condition in which fluid-filled cavities (syringes) form and expand in the spinal cord. Syringomyelia is often linked with obstruction of the craniocervical junction and a Chiari malformation, which is similar in both humans and animals. Some brachycephalic toy breed dogs such as Cavalier King Charles Spaniels (CKCS) are particularly predisposed. The exact mechanism of the formation of syringomyelia is undetermined and consequently with the lack of clinical explanation, engineers and mathematicians have resorted to computer models to identify possible physical mechanisms that can lead to syringes. We developed a computer model of the spinal cavity of a CKCS suffering from a large syrinx. The model was excited at the cranial end to simulate the movement of the cerebrospinal fluid (CSF) and the spinal cord due to the shift of blood volume in the cranium related to the cardiac cycle. To simulate the normal condition, the movement was prescribed to the CSF. To simulate the pathological condition, the movement of CSF was blocked

Mass-Losing Semiregular Variable Stars in Baade's Windows

By cross-correlating the results of two recent large-scale surveys, the general properties of a well defined sample of semi-regular variable stars have been determined. ISOGAL mid-infrared photometry and MACHO lightcurves are assembled for approximately 300 stars in the Baade's Windows of low extinction towards the Galactic bulge. These stars are mainly giants of late M spectral type, evolving along the asymptotic giant branch (AGB). They are found to possess a wide and continuous distribution of pulsation periods and to obey an approximate log~period -- bolometric magnitude relation or set of such relations. Approximate mass-loss rates in the range of 1e-8 to 5e-7 M_sun per year are derived from ISOGAL mid-infrared photometry and models of stellar spectra adjusted for the presence of optically-thin circumstellar silicate dust. Mass-loss rates depend on luminosity and pulsation period. Some stars lose mass as rapidly as short-period Miras but do not show Mira-like amplitudes. A period of 70 days or longer is a necessary but not a sufficient condition for mass loss to occur. For AGB stars in the mass-loss ranges that we observe, the functional dependence of mass-loss rate on temperature and luminosity is found to be in agreement with recent theoretical predictions. If we include our mass-loss rates with a sample of extreme mass-losing AGB stars in the Large Magellanic Cloud, we get the general result for AGB stars that mass-loss rate is proportional to luminosity^{2.7}, valid for AGB stars with 10^{-8} to 10^{-4} M_sun per year (Abridged).Comment: to appear in The Astrophysical Journal, 51 pages, 9 figures, 3 tables; table 1 will be available in machine-readable format at the electronic Ap

Codes for the Quantum Erasure Channel

The quantum erasure channel (QEC) is considered. Codes for the QEC have to correct for erasures, i. e., arbitrary errors at known positions. We show that four qubits are necessary and sufficient to encode one qubit and correct one erasure, in contrast to five qubits for unknown positions. Moreover, a family of quantum codes for the QEC, the quantum BCH codes, that can be efficiently decoded is introduced.Comment: 6 pages, RevTeX, no figures, submitted to Physical Review A, code extended to encode 2 qubits, references adde

Ultrafast optical control of entanglement between two quantum dot spins

The interaction between two quantum bits enables entanglement, the two-particle correlations that are at the heart of quantum information science. In semiconductor quantum dots much work has focused on demonstrating single spin qubit control using optical techniques. However, optical control of entanglement of two spin qubits remains a major challenge for scaling from a single qubit to a full-fledged quantum information platform. Here, we combine advances in vertically-stacked quantum dots with ultrafast laser techniques to achieve optical control of the entangled state of two electron spins. Each electron is in a separate InAs quantum dot, and the spins interact through tunneling, where the tunneling rate determines how rapidly entangling operations can be performed. The two-qubit gate speeds achieved here are over an order of magnitude faster than in other systems. These results demonstrate the viability and advantages of optically controlled quantum dot spins for multi-qubit systems.Comment: 24 pages, 5 figure

A new, large-bodied omnivorous bat (Noctilionoidea: Mystacinidae) reveals lost morphological and ecological diversity since the Miocene in New Zealand

A new genus and species of fossil bat is described from New Zealand's only pre-Pleistocene Cenozoic terrestrial fauna, the early Miocene St Bathans Fauna of Central Otago, South Island. Bayesian total evidence phylogenetic analysis places this new Southern Hemisphere taxon among the burrowing bats (mystacinids) of New Zealand and Australia, although its lower dentition also resembles Africa's endemic sucker-footed bats (myzopodids). As the first new bat genus to be added to New Zealand's fauna in more than 150 years, it provides new insight into the original diversity of chiropterans in Australasia. It also underscores the significant decline in morphological diversity that has taken place in the highly distinctive, semi-terrestrial bat family Mystacinidae since the Miocene. This bat was relatively large, with an estimated body mass of ~40 g, and its dentition suggests it had an omnivorous diet. Its striking dental autapomorphies, including development of a large hypocone, signal a shift of diet compared with other mystacinids, and may provide evidence of an adaptive radiation in feeding strategy in this group of noctilionoid bats

Two's Company, Three's a Crowd: Experimental Evaluation of the Evolutionary Maintenance of Trioecy in Mercurialis annua (Euphorbiaceae)

Trioecy is an uncommon sexual system in which males, females, and hermaphrodites co-occur as three clearly different gender classes. The evolutionary stability of trioecy is unclear, but would depend on factors such as hermaphroditic sex allocation and rates of outcrossing vs. selfing. Here, trioecious populations of Mercurialis annua are described for the first time. We examined the frequencies of females, males and hermaphrodites across ten natural populations and evaluated the association between the frequency of females and plant densities. Previous studies have shown that selfing rates in this species are density-dependent and are reduced in the presence of males, which produce substantially more pollen than hermaphrodites. Accordingly, we examined the evolutionary stability of trioecy using an experiment in which we (a) indirectly manipulated selfing rates by altering plant densities and the frequency of males in a fully factorial manner across 20 experimental plots and (b) examined the effect of these manipulations on the frequency of the three sex phenotypes in the next generation of plants. In the parental generation, we measured the seed and pollen allocations of hermaphrodites and compared them with allocations by unisexual plants. In natural populations, females occurred at higher frequencies in denser patches, a finding consistent with our expectations. Under our experimental conditions, however, no combination of plant densities and male frequencies was associated with increased frequencies of females. Our results suggest that the factors that regulate female frequencies in trioecious populations of M. annua are independent of those regulating male frequencies (density), and that the stable co-existence of all three sex phenotypes within populations is unlikely

The influence of the accessory genome on bacterial pathogen evolution

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations