CAMP: A Common API for Measuring Performance

Accurate performance testing of heterogeneous distributed systems, such as those created using GRID technology, requires a consistent method for retrieving system performance data from multiple platforms. This paper presents CAMP: a low-level platform independent performance data API designed for use with distributed testing frameworks. CAMP is not necessarily tied to the distributed testing task: it provides a simple, low-level interface into operating system performance data that can be used to build complex performance measurement applications. This paper discusses CAMP\u27s functionality and implementation in detail. It also contains a detailed analysis of the API\u27s correctness, performance, and overhead

Quantifying CD8+ T cell dynamics in infectious diseases

CD8+ T cells are an important part of the adaptive immune system. They are not only able to efficiently kill infected cells, but can also provide protection against subsequent infections. Recently, T cell-based vaccines, which are able to elicit protection-mediating CD8+ T cell responses, have shown their potential against various infectious diseases, including malaria or HIV. However, the efficient implementation of these approaches is currently hampered by a lack of knowledge regarding the dynamical processes generating the protective responses. In this thesis, we combined experimental data and mathematical modelling to analyse and quantify CD8+ T cell dynamics in different infectious diseases. First, we study a specific immune responses elicited by cytomegalovirus (CMV) infection, known as 'memory in ation'. We used mathematical modelling to test different hypotheses regarding the processes that generate and maintain memory in ation and analysed how viral dynamics shape the corresponding CD8+ T cell responses. Since CMV has already been used as a vaccine vector expressing foreign epitopes, our findings are relevant for improving the efficacy of these vector-based vaccination approaches. To generate sufficient protection, vaccination strategies usually require the application of one or more booster injections. Here, factors such as dosage, frequency and timing of injections can influence the protective levels reached. To determine the impact of current vaccination strategies against malaria, we analysed the in uence of vaccination regimens, differing in dosage and frequency of injections, on the generation of organ-specific CD8+ T cell responses. We identified the underlying cellular differentiation and migration pathway and determined the impact of different vaccination doses on the build-up and maintenance of protection-mediating liver-resident memory cells. Our results do not only provide a quantitative understanding of CD8+ T cell responses elicited by immunisation, but can also be used to improve existing vaccination approaches. Understanding the impact of T cell-based vaccination regimes on the immune system requires knowledge about the underlying cellular dynamics. While mathematical modelling allows the determination of differentiation pathways and the quantification of cellular turnover, the reliability of these analyses depends strongly on the quality of the available data. While the labelling of cells has been a useful method to increase the amount of information within cellular data, it has not been analysed so far how the design of applied labelling strategies aspects the mathematical estimation of cellular turnover. To this end, we determined the robustness of different labelling strategies to infer cellular dynamics including data suffering from experimental limitations. Our fndings can be used as a guideline to determine cellular dynamics more accurately in future experiments. In summary, by combining experimental data and mathematical modelling our results do not provide a quantitative understanding of CD8+ T cell responses in infectious diseases, but can also be used to improve the efficiency and efficacy of T cell-based vaccines

Potent spinal parenchymal AAV9-mediated gene delivery by subpial injection in adult rats and pigs.

Effective in vivo use of adeno-associated virus (AAV)-based vectors to achieve gene-specific silencing or upregulation in the central nervous system has been limited by the inability to provide more than limited deep parenchymal expression in adult animals using delivery routes with the most clinical relevance (intravenous or intrathecal). Here, we demonstrate that the spinal pia membrane represents the primary barrier limiting effective AAV9 penetration into the spinal parenchyma after intrathecal AAV9 delivery. We develop a novel subpial AAV9 delivery technique and AAV9-dextran formulation. We use these in adult rats and pigs to show (i) potent spinal parenchymal transgene expression in white and gray matter including neurons, glial and endothelial cells after single bolus subpial AAV9 delivery; (ii) delivery to almost all apparent descending motor axons throughout the length of the spinal cord after cervical or thoracic subpial AAV9 injection; (iii) potent retrograde transgene expression in brain motor centers (motor cortex and brain stem); and (iv) the relative safety of this approach by defining normal neurological function for up to 6 months after AAV9 delivery. Thus, subpial delivery of AAV9 enables gene-based therapies with a wide range of potential experimental and clinical utilizations in adult animals and human patients

The Narrow-Line Regions of LINERs as Resolved with the Hubble Space Telescope

LINERs exist in the nuclei of a large fraction of luminous galaxies, but their connection with the AGN phenomenon has remained elusive. We present Hubble Space Telescope narrowband [O III]5007 and H-alpha+[N II] emission-line images of the central regions of 14 galaxies with LINER nuclei. The compact, ~1 arcsec-scale, unresolved emission that dominates the line flux in ground-based observations is mostly resolved by HST. The bulk of this emission comes from regions with sizes of tens to hundreds of parsecs that are resolved into knots, filaments, and diffuse gas whose morphology differs from galaxy to galaxy. Most of the galaxies do not show clear linear structures or ionization cones analogous to those often seen in Seyfert galaxies. An exception is NGC 1052, the prototypical LINER, in which we find a 3 arcsec-long (~ 250 pc) biconical structure that is oriented on the sky along the galaxy's radio jet axis. Seven of the galaxies have been shown in previously published HST images to have a bright compact ultraviolet nuclear source, while the other seven do not have a central UV source. Our images find evidence of dust in the nuclear regions of all 14 galaxies, with clear indications of nuclear obscuration in most of the "UV-dark" cases. The data suggest that the line-emitting gas in most LINERs is photoionized by a central source (which may be stellar, nonstellar, or a combination thereof) but that this source is often hidden from direct view. We find no obvious morphological differences between LINERs with detected weak broad H-alpha wings in their spectra and those with only narrow lines. Likewise, there is no clear morphological distinction between objects whose UV spectra are dominated by hot stars (e.g., NGC 4569) and those that are AGN-like (e.g., NGC 4579).Comment: Accepted for publication in the ApJ. 25 pages, 3 tables, 9 JPEG Figure

The Physical Conditions of the Intrinsic N V Narrow Absorption Line Systems of Three Quasars

We employ detailed photoionization models to infer the physical conditions of intrinsic narrow absorption line systems found in high resolution spectra of three quasars at z=2.6-3.0. We focus on a family of intrinsic absorbers characterized by N V lines that are strong relative to the Ly-alpha lines. The inferred physical conditions are similar for the three intrinsic N V absorbers, with metallicities greater than 10 times the solar value (assuming a solar abundance pattern), and with high ionization parameters (log U ~ 0). Thus, we conclude that the unusual strength of the N V lines results from a combination of partial coverage, a high ionization state, and high metallicity. We consider whether dilution of the absorption lines by flux from the broad-emission line region can lead us to overestimate the metallicities and we find that this is an unlikely possibility. The high abundances that we infer are not surprising in the context of scenarios in which metal enrichment takes place very early on in massive galaxies. We estimate that the mass outflow rate in the absorbing gas (which is likely to have a filamentary structure) is less than a few solar masses per year under the most optimistic assumptions, although it may be embedded in a much hotter, more massive outflow.Comment: To appear in the Astrophysical Journa

Trust, Trust Repair, and Public Health: A Scoping Review Protocol

Trust can be defined as “a willingness to be vulnerable to another for a given set of tasks” and thus, trust and public health are inextricably linked. State actors are key participants in population health, organizing, among other things, mandates and guidelines that target health behaviors and encourage the uptake of medicines, screenings, diagnostics, and control of health conditions. Effective implementation of these crucial, government-sponsored health efforts is conditional on the public’s belief that the state is trustworthy and has one\u27s best interest in mind – positioning trust in government as a central determinant of public health. Trusting relationships between patients, health systems, and health care providers are also essential, as high-quality, safe care and adherence with healthcare professionals’ recommendations heavily depend upon trust. In many countries, trust in government and health care providers are inseparable, as governments are the primary providers of healthcare. Despite these critical relationships, existing studies that link trust and public health outcomes often focus on contemporaneous factors, many of which are endogenous to public health outcomes (e.g., support for the incumbent political party). For example, Sopory and colleagues reported a comprehensive examination of the phenomenon of trust during public health emergency events among 68 studies from 28 countries that included individuals who were directly affected by a public health emergency. Importantly, no studies from South America or Africa were included. The shortage of research on the sociostructural, historical, economic, and political sources of low trust limits our understanding of how trust deficits might be remedied so as to improve population health. Understanding why trust is low as well as how to repair trust are thus of critical importance

The Ionized Gas and Nuclear Environment in NGC 3783 V. Variability and Modeling of the Intrinsic Ultraviolet Absorption

We present results on the location, physical conditions, and geometry of the outflow in the Seyfert 1 galaxy NGC 3783 from a study of the variable intrinsic UV absorption. Based on 18 observations with HST/STIS and 6 observations with FUSE, we find: 1) The absorption from the lowest-ionization species in each of the three strong kinematic components varied inversely with the continuum flux, indicating the ionization structure responded to changes in the photoionizing flux over the weekly timescales sampled by our observations. 2) A multi- component model with an unocculted NLR and separate BLR and continuum line-of-sight covering factors predicts saturation in several lines, consistent with the lack of observed variability. 3) Column densities for the individual metastable levels are measured from the resolved C III *1175 absorption complex observed in one component. Based on our computed metastable level populations, the electron density of this absorber is ~3x10^4 cm^-3. Photoionization modeling results place it at ~25 pc from the central source. 4) Using time-dependent calculations, we are able to reproduce the detailed variability observed in this absorber, and derive upper limits on the distances for the other components of 25-50 pc. 5) The ionization parameters derived for the higher ionization UV absorbers are consistent with the modeling results for the lowest-ionization X-ray component, but with smaller total column density. They have similar pressures as the three X-ray ionization components. These results are consistent with an inhomogeneous wind model for the outflow in NGC 3783. 6) Based on the predicted emission-line luminosities, global covering factor constraints, and distances derived for the UV absorbers, they may be identified with emission- line gas observed in the inner NLR of AGNs. (abridged)Comment: 30 pages, 18 figures (7 color), emulateapj, accepted for publication in The Astrophysical Journa

Functional Organization of a Neural Network for Aversive Olfactory Learning in Caenorhabditis elegans

Many animals use their olfactory systems to learn to avoid dangers, but how neural circuits encode naive and learned olfactory preferences, and switch between those preferences, is poorly understood. Here, we map an olfactory network, from sensory input to motor output, which regulates the learned olfactory aversion of Caenorhabditis elegans for the smell of pathogenic bacteria. Naive animals prefer smells of pathogens but animals trained with pathogens lose this attraction. We find that two different neural circuits subserve these preferences, with one required for the naive preference and the other specifically for the learned preference. Calcium imaging and behavioral analysis reveal that the naive preference reflects the direct transduction of the activity of olfactory sensory neurons into motor response, whereas the learned preference involves modulations to signal transduction to downstream neurons to alter motor response. Thus, two different neural circuits regulate a behavioral switch between naive and learned olfactory preferences.Organismic and Evolutionary BiologyPhysic