Herschel-PACS observation of the 10 Myr old T Tauri disk TW Hya: Constraining the disk gas mass

Planets are formed in disks around young stars. With an age of ~10 Myr, TW Hya is one of the nearest T Tauri stars that is still surrounded by a relatively massive disk. In addition a large number of molecules has been found in the TWHya disk, making TWHya the perfect test case in a large survey of disks with Herschel–PACS to directly study their gaseous component. We aim to constrain the gas and dust mass of the circumstellar disk around TW Hya. We observed the fine-structure lines of [O_I] and [C_(II)] as part of the open-time large program GASPS. We complement this with continuum data and ground-based ^(12)CO 3–2 and ^(13)CO 3–2 observations. We simultaneously model the continuum and the line fluxes with the 3D Monte-Carlo code MCFOST and the thermo-chemical code ProDiMo to derive the gas and dust masses. We detect the [O_I] line at 63 μm. The other lines that were observed, [O_I] at 145 μm and [C_(II)] at 157 μm, are not detected. No extended emission has been found. Preliminary modeling of the photometric and line data assuming [^(12)CO]/[^(13)CO] = 69 suggests a dust mass for grains with radius <1 mm of ~1.9 × 10^(−4) M_⊙ (total solid mass of 3 × 10^(−3) M_⊙) and a gas mass of (0.5–5) ×10^(−3) M_⊙. The gas-to-dust mass may be lower than the standard interstellar value of 100

Determinant of HIV-1 mutational escape from cytotoxic T lymphocytes.

CD8+ class I-restricted cytotoxic T lymphocytes (CTLs) usually incompletely suppress HIV-1 in vivo, and while analogous partial suppression induces antiretroviral drug-resistance mutations, epitope escape mutations are inconsistently observed. However, escape mutation depends on the net balance of selective pressure and mutational fitness costs, which are poorly understood and difficult to study in vivo. Here we used a controlled in vitro system to evaluate the ability of HIV-1 to escape from CTL clones, finding that virus replicating under selective pressure rapidly can develop phenotypic resistance associated with genotypic changes. Escape varied between clones recognizing the same Gag epitope or different Gag and RT epitopes, indicating the influence of the T cell receptor on pressure and fitness costs. Gag and RT escape mutations were monoclonal intra-epitope substitutions, indicating limitation by fitness constraints in structural proteins. In contrast, escape from Nef-specific CTL was more rapid and consistent, marked by a polyclonal mixture of epitope point mutations and upstream frameshifts. We conclude that incomplete viral suppression by CTL can result in rapid emergence of immune escape, but the likelihood is strongly determined by factors influencing the fitness costs of the particular epitope targeted and the ability of responding CTL to recognize specific epitope variants

A heparin-mimicking polymer conjugate stabilizes basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) is a protein that plays a crucial role in diverse cellular functions, from wound healing to bone regeneration. However, a major obstacle to the widespread application of bFGF is its inherent instability during storage and delivery. Here, we describe the stabilization of bFGF by covalent conjugation with a heparin-mimicking polymer, a copolymer consisting of styrene sulfonate units and methyl methacrylate units bearing poly(ethylene glycol) side chains. The bFGF conjugate of this polymer retained bioactivity after synthesis and was stable to a variety of environmentally and therapeutically relevant stressors--such as heat, mild and harsh acidic conditions, storage and proteolytic degradation--unlike native bFGF. Following the application of stress, the conjugate was also significantly more active than the control conjugate system in which the styrene sulfonate units were omitted from the polymer structure. This research has important implications for the clinical use of bFGF and for the stabilization of heparin-binding growth factors in general

Healthcare use for diarrhoea and dysentery in actual and hypothetical cases, Nha Trang, Viet Nam.

To better understand healthcare use for diarrhoea and dysentery in Nha Trang, Viet Nam, qualitative interviews with community residents and dysentery case studies were conducted. Findings were supplemented by a quantitative survey which asked respondents which healthcare provider their household members would use for diarrhoea or dysentery. A clear pattern of healthcare-seeking behaviours among 433 respondents emerged. More than half of the respondents self-treated initially. Medication for initial treatment was purchased from a pharmacy or with medication stored at home. Traditional home treatments were also widely used. If no improvement occurred or the symptoms were perceived to be severe, individuals would visit a healthcare facility. Private medical practitioners are playing a steadily increasing role in the Vietnamese healthcare system. Less than a quarter of diarrhoea patients initially used government healthcare providers at commune health centres, polyclinics, and hospitals, which are the only sources of data for routine public-health statistics. Given these healthcare-use patterns, reported rates could significantly underestimate the real disease burden of dysentery and diarrhoea