Detection of Ne VIII in the Low-Redshift Warm-Hot IGM

High resolution FUSE and STIS observations of the bright QSO HE 0226-4110 (zem = 0.495) reveal the presence of a multi-phase absorption line system at zabs(O VI) = 0.20701 containing absorption from H I (Ly alpha to Ly theta), C III, O III, O IV, O VI, N III, Ne VIII, Si III, S VI and possibly S V. Single component fits to the Ne VIII and O VI absorption doublets yield logN(Ne VIII) = 13.89+/-0.11 and logN(O VI) = 14.37+/-0.03. The Ne VIII and O VI doublets are detected at 3.9 sigma and 16 sigma significance levels, respectively. This represents the first detection of intergalactic Ne VIII, a diagnostic of gas with temperature in the range from 5x10(5) to 1x10(6) K. The O VI and Ne VIII are not likely created in a low density medium photoionized solely by the extragalactic background at z = 0.2 since the required path length of ~11 Mpc implies the Hubble flow absorption line broadening would be ~10 times greater than the observed line widths. A collisional ionization origin is therefore more likely. Assuming [Ne/H] and [O/H] = -0.5, the value N(Ne VIII)/N(O VI) = 0.33+/-0.10 is consistent with gas in collisional ionization equilibrium near T=5.4x10(5) K with logN(H)= 19.9 and N(H)/N(H I) = 1.7x10(6). The observations support the basic idea that a substantial fraction of the baryonic matter at low redshift exists in hot very highly ionized gaseous structures.Comment: 32 pages text and 9 pages of figures. Accepted by the Astrophysical Journa

Mouse Models of Prostate Cancer

The development and optimization of high-throughput screening methods has identified a multitude of genetic changes associated with human disease. The use of immunodeficient and genetically engineered mouse models that mimic the human disease has been crucial in validating the importance of these genetic pathways in prostate cancer. These models provide a platform for finding novel therapies to treat human patients afflicted with prostate cancer as well as those who have debilitating bone metastases. In this paper, we focus on the historical development and phenotypic descriptions of mouse models used to study prostate cancer. We also comment on how closely each model recapitulates human prostate cancer

A role for glycolipid biosynthesis in severe fever with thrombocytopenia syndrome virus entry

A novel bunyavirus was recently found to cause severe febrile illness with high mortality in agricultural regions of China, Japan, and South Korea. This virus, named severe fever with thrombocytopenia syndrome virus (SFTSV), represents a new group within the Phlebovirus genus of the Bunyaviridae. Little is known about the viral entry requirements beyond showing dependence on dynamin and endosomal acidification. A haploid forward genetic screen was performed to identify host cell requirements for SFTSV entry. The screen identified dependence on glucosylceramide synthase (ugcg), the enzyme responsible for initiating de novo glycosphingolipid biosynthesis. Genetic and pharmacological approaches confirmed that UGCG expression and enzymatic activity were required for efficient SFTSV entry. Furthermore, inhibition of UGCG affected a post-internalization stage of SFTSV entry, leading to the accumulation of virus particles in enlarged cytoplasmic structures, suggesting impaired trafficking and/or fusion of viral and host membranes. These findings specify a role for glucosylceramide in SFTSV entry and provide a novel target for antiviral therapies

Molecular Hydrogen in High-Velocity Clouds

We present Far Ultraviolet Spectroscopic Explorer (FUSE) observations of interstellar molecular hydrogen (H_2) in two Galactic high-velocity clouds (HVCs). Molecular hydrogen absorption is detected in the Magellanic Stream (abundance ~0.3 solar) toward the Seyfert galaxy Fairall 9 in the lowest three rotational states (J=0-2) at v(LSR)=+190 km/s, yielding a total H_2 column density of log N(H_2)=16.40(+0.26)(-0.53). In contrast, no H_2 absorption is seen in the high-velocity cloud Complex C (abundance ~0.1 solar) toward the quasar PG 1259+593 (log N(H_2)<13.96 at v(LSR)=-130 km/s) although both HVCs have similar HI column densities on the order of log N(HI)~20. Weak H_2 absorption is detected in the Intermediate-Velocity Arch (IV Arch; abundance \~1.0 solar) toward PG 1259+593 (log N(H_2)=14.10(+0.21)(-0.44) at v(LSR)=-55 km/s and log N(HI)=19.5). It thus appears that metal- and dust-poor halo clouds like Complex C are not able to form and maintain widely distributed H_2, whereas metal and dust-rich halo clouds like the IV Arch can maintain H_2 even at low HI column densities.Comment: 12 pages, 3 figures; Accepted for publication in ApJ Letter

THE INFLUENCE OF THIRD GENERATION ARTIFICIAL SOCCER TURF CHARACTERISTICS ON GROUND REACTION FORCES DURING RUNNING

The aim of this study was to determine the effect of different artificial soccer turf pitches on the ground reaction forces of running soccer players. For this purpose ground reaction forces were determined for twenty soccer players while they ran at three different speeds across a 25 meter long track covered with a third generation artificial soccer turf. Three different pitches, two FIFA 1star and one FIFA 2star, were examined. There was no difference between the two 1star systems in the peak vertical and horizontal ground reactions forces. Data on the 2star system was equivocal due to a too small sample size. It is concluded that surface characteristics influence the loading of the human muscle-skeletal system more subtly than initially anticipated. A more detailed biomechanical analysis of the events during impact is required to identify the critical loading parameters

What Brown Saw and You Can Too

A discussion of Robert Brown’s original observations of particles ejected by pollen of the plant Clarkia pulchella undergoing what is now called Brownian motion is given. We consider the nature of those particles and how he misinterpreted the Airy disk of the smallest particles to be universal organic building blocks. Relevant qualitative and quantitative investigations with a modern microscope and with a “homemade” single lens microscope similar to Brown’s are presented

Structural basis of IL-23 antagonism by an Alphabody protein scaffold

Protein scaffolds can provide a promising alternative to antibodies for various biomedical and biotechnological applications, including therapeutics. Here we describe the design and development of the Alphabody, a protein scaffold featuring a single-chain antiparallel triple-helix coiled-coil fold. We report affinity-matured Alphabodies with favourable physicochemical properties that can specifically neutralize human interleukin (IL)-23, a pivotal therapeutic target in autoimmune inflammatory diseases such as psoriasis and multiple sclerosis. The crystal structure of human IL-23 in complex with an affinity-matured Alphabody reveals how the variable interhelical groove of the scaffold uniquely targets a large epitope on the p19 subunit of IL-23 to harness fully the hydrophobic and hydrogen-bonding potential of tryptophan and tyrosine residues contributed by p19 and the Alphabody, respectively. Thus, Alphabodies are suitable for targeting protein-protein interfaces of therapeutic importance and can be tailored to interrogate desired design and binding-mode principles via efficient selection and affinity-maturation strategies