P19-26. Directing macaque immune responses with an anti-dendritic cell HIV Gag p24 fusion protein vaccine

International audiencen.

PRACTICAL DESIGN EXAMPLES FOR HUMAN HABITATS IN SPACE, OFF-GRID, AND IN LOW-IMPACT COMMUNITIES

All human habitat problems fall into three major categories- the environment, the habitat itself, and the occupants. By breaking these problems down into common themes and addressing them directly, we can build a common knowledge base for all three challenges faced by humanity. A crew living in space has the new problems of coping with radiation, microgravity, and vacuum. All the while, they are dealing the usual issues of eating, sleeping, and getting along with the rest of the occupants. By isolating the differences between space and earth habitats, we can create common architectural styles for each human habitat challenge where commonality is appropriate. We can then examine the differences, then isolate and modularize the secondary systems where possible. This simplifies experimentation and testing of the physical and psychological design of a structure on Earth prior to attempting use in space. It also allows spin-off architectures for extreme environments, off-grid settlements, research bases, and low impact communities on Earth. By isolating and testing each attribute of the system in parallel with control groups, we can scientifically refine the systems for human shelter regardless of environment. This paper will show numerous examples of architectures designed for space or space analog research bases. These designs can be both de-scoped to off-grid sustainable architecture, and scoped up for space habitat applications. Concepts such as internal greenhouses, enclosed permaculture, thermal protection, energy management, and radiation shielding are included for both minimal habitats and large bases. These systems can then be applied for disaster first responders, research bases in extreme environments, o-grid homes, and low-impact communities

Second Generation Leptoquark Search in p\bar{p} Collisions at s\sqrt{s} = 1.8 TeV

We report on a search for second generation leptoquarks with the D\O\ detector at the Fermilab Tevatron $p\bar{p}$ collider at $\sqrt{s}$ = 1.8 TeV. This search is based on 12.7 pb$^{-1}$ of data. Second generation leptoquarks are assumed to be produced in pairs and to decay into a muon and quark with branching ratio $\beta$ or to neutrino and quark with branching ratio $(1-\beta)$. We obtain cross section times branching ratio limits as a function of leptoquark mass and set a lower limit on the leptoquark mass of 111 GeV/c$^{2}$ for $\beta = 1$ and 89 GeV/c$^{2}$ for $\beta = 0.5$ at the 95%\ confidence level.Comment: 18 pages, FERMILAB-PUB-95/185-

Jet Production via Strongly-Interacting Color-Singlet Exchange in ppˉp\bar{p} Collisions

A study of the particle multiplicity between jets with large rapidity separation has been performed using the D{\O}detector at the Fermilab Tevatron $p\bar{p}$ Collider operating at $\sqrt{s}=1.8$ TeV. A significant excess of low-multiplicity events is observed above the expectation for color-exchange processes. The measured fractional excess is $1.07 \pm 0.10({\rm stat})^{+ 0.25}_{- 0.13}({\rm syst})$, which is consistent with a strongly-interacting color-singlet (colorless) exchange process and cannot be explained by electroweak exchange alone. A lower limit of 0.80% (95% C.L.) is obtained on the fraction of dijet events with color-singlet exchange, independent of the rapidity gap survival probability.Comment: 15 pages (REVTeX), 3 PS figs (uuencoded/tar compressed, epsf.sty) Complete postscript available at http://d0sgi0.fnal.gov/d0pubs/journals.html Submitted to Physical Review Letter

Decay in survival motor neuron and plastin 3 levels during differentiation of iPSC-derived human motor neurons

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by mutations in Survival Motor Neuron 1 (SMN1), leading to degeneration of alpha motor neurons (MNs) but also affecting other cell types. Induced pluripotent stem cell (iPSC)-derived human MN models from severe SMA patients have shown relevant phenotypes. We have produced and fully characterized iPSCs from members of a discordant consanguineous family with chronic SMA. We differentiated the iPSC clones into ISL-1+/ChAT+ MNs and performed a comparative study during the differentiation process, observing significant differences in neurite length and number between family members. Analyses of samples from wild-type, severe SMA type I and the type IIIa/IV family showed a progressive decay in SMN protein levels during iPSC-MN differentiation, recapitulating previous observations in developmental studies. PLS3 underwent parallel reductions at both the transcriptional and translational levels. The underlying, progressive developmental decay in SMN and PLS3 levels may lead to the increased vulnerability of MNs in SMA disease. Measurements of SMN and PLS3 transcript and protein levels in iPSC-derived MNs show limited value as SMA biomarkers

Are motor inhibition and cognitive flexibility dead ends in ADHD?

Contains fulltext : 53518.pdf (publisher's version ) (Closed access)Executive dysfunction has been postulated as the core deficit in ADHD, although many deficits in lower order cognitive processes have also been identified. By obtaining an appropriate baseline of lower order cognitive functioning light may be shed on as to whether executive deficits result from problems in lower order and/or higher order cognitive processes. We examined motor inhibition and cognitive flexibility in relation to a baseline measure in 816 children from ADHD and control families. Multiple children in a family were tested in order to examine the familiality of the measures. No evidence was found for deficits in motor inhibition or cognitive flexibility in children with ADHD or their nonaffected siblings: Compared to their baseline speed and accuracy of responding, children with ADHD and their (non)affected siblings were not disproportionally slower or inaccurate when demands for motor inhibition or cognitive flexibility were added to the task. However, children with ADHD and their (non)affected siblings were overall less accurate than controls, which could not be attributed to differences in response speed. This suggests that inaccuracy of responding is characteristic of children having (a familial risk for) ADHD. Motor inhibition and cognitive flexibility as operationalized with mean reaction time were found to be familial. It is concluded that poorer performance on executive tasks in children with ADHD and their (non)affected siblings may result from deficiencies in lower order cognitive processes and not (only) from higher order cognitive processes/executive functions

IRGM Is a Common Target of RNA Viruses that Subvert the Autophagy Network

Autophagy is a conserved degradative pathway used as a host defense mechanism against intracellular pathogens. However, several viruses can evade or subvert autophagy to insure their own replication. Nevertheless, the molecular details of viral interaction with autophagy remain largely unknown. We have determined the ability of 83 proteins of several families of RNA viruses (Paramyxoviridae, Flaviviridae, Orthomyxoviridae, Retroviridae and Togaviridae), to interact with 44 human autophagy-associated proteins using yeast two-hybrid and bioinformatic analysis. We found that the autophagy network is highly targeted by RNA viruses. Although central to autophagy, targeted proteins have also a high number of connections with proteins of other cellular functions. Interestingly, immunity-associated GTPase family M (IRGM), the most targeted protein, was found to interact with the autophagy-associated proteins ATG5, ATG10, MAP1CL3C and SH3GLB1. Strikingly, reduction of IRGM expression using small interfering RNA impairs both Measles virus (MeV), Hepatitis C virus (HCV) and human immunodeficiency virus-1 (HIV-1)-induced autophagy and viral particle production. Moreover we found that the expression of IRGM-interacting MeV-C, HCV-NS3 or HIV-NEF proteins per se is sufficient to induce autophagy, through an IRGM dependent pathway. Our work reveals an unexpected role of IRGM in virus-induced autophagy and suggests that several different families of RNA viruses may use common strategies to manipulate autophagy to improve viral infectivity