Argumentation in biology : exploration and analysis through a gene expression use case

Argumentation theory conceptualises the human practice of debating. Implemented as computational argumentation it enables a computer to perform a virtual debate. Using existing knowledge from research into argumentation theory, this thesis investigates the potential of computational argumentation within biology. As a form of non-monotonic reasoning, argumentation can be used to tackle inconsistent and incomplete information - two common problems for the users of biological data. Exploration of argumentation shall be conducted by examining these issues within one biological subdomain: in situ gene expression information for the developmental mouse. Due to the complex and often contradictory nature of biology, occasionally it is not apparent whether or not a particular gene is involved in the development of a particular tissue. Expert biological knowledge is recorded, and used to generate arguments relating to this matter. These arguments are presented to the user in order to help him/her decide whether or not the gene is expressed. In order to do this, the notion of argumentation schemes has been borrowed from philosophy, and combined with ideas and technologies from arti cial intelligence. The resulting conceptualisation is implemented and evaluated in order to understand the issues related to applying computational argumentation within biology. Ultimately, this work concludes with a discussion of Argudas - a real world tool developed for the biological community, and based on the knowledge gained during this work

Comparative ergonomic workflow and user experience analysis of MRI versus fluoroscopy-guided vascular interventions:an iliac angioplasty exemplar case study

Purpose A methodological framework is introduced to assess and compare a conventional fluoroscopy protocol for peripheral angioplasty with a new magnetic resonant imaging (MRI)-guided protocol. Different scenarios were considered during interventions on a perfused arterial phantom with regard to time-based and cognitive task analysis, user experience and ergonomics. Methods Three clinicians with different expertise performed a total of 43 simulated common iliac angioplasties (9 fluoroscopic, 34 MRI-guided) in two blocks of sessions. Six different configurations for MRI guidance were tested in the first block. Four of them were evaluated in the second block and compared to the fluoroscopy protocol. Relevant stages’ durations were collected, and interventions were audio-visually recorded from different perspectives. A cued retrospective protocol analysis (CRPA) was undertaken, including personal interviews. In addition, ergonomic constraints in the MRI suite were evaluated. Results Significant differences were found when comparing the performance between MRI configurations versus fluoroscopy. Two configurations [with times of 8.56 (0.64) and 9.48 (1.13) min] led to reduce procedure time for MRI guidance, comparable to fluoroscopy [8.49 (0.75) min]. The CRPA pointed out the main influential factors for clinical procedure performance. The ergonomic analysis quantified musculoskeletal risks for interventional radiologists when utilising MRI. Several alternatives were suggested to prevent potential low-back injuries. Conclusions This work presents a step towards the implementation of efficient operational protocols for MRI-guided procedures based on an integral and multidisciplinary framework, applicable to the assessment of current vascular protocols. The use of first-user perspective raises the possibility of establishing new forms of clinical training and education

Durability and inflammogenic impact of carbon nanotubes compared with asbestos fibres

<p>Abstract</p> <p>Background</p> <p>It has been suggested that carbon nanotubes might conform to the fibre pathogenicity paradigm that explains the toxicities of asbestos and other fibres on a continuum based on length, aspect ratio and biopersistence. Some types of carbon nanotubes satisfy the first two aspects of the fibre paradigm but only recently has their biopersistence begun to be investigated. Biopersistence is complex and requires <it>in vivo </it>testing and analysis. However durability, the chemical mimicking of the process of fibre dissolution using <it>in vitro </it>treatment, is closely related to biopersistence and more readily determined. Here, we describe an experimental process to determine the durability of four types of carbon nanotubes in simulated biological fluid (Gambles solution), and their subsequent pathogenicity <it>in vivo </it>using a mouse model sensitive to inflammogenic effects of fibres. The <it>in vitro </it>and <it>in vivo </it>results were compared with well-characterised glass wool and asbestos fibre controls.</p> <p>Results</p> <p>After incubation for up to 24 weeks in Gambles solution, our control fibres were recovered at percentages consistent with their known <it>in vitro </it>durabilities and/or <it>in vivo </it>persistence, and three out of the four types of carbon nanotubes tested (single-walled (CNT_SW) and multi-walled (CNT_TANG2, CNT_SPIN)) showed no, or minimal, loss of mass or change in fibre length or morphology when examined by electron microscopy. However, the fourth type [multi-walled (CNT_LONG1)] lost 30% of its original mass within the first three weeks of incubation, after which there was no further loss. Electron microscopy of CNT_LONG1samples incubated for 10 weeks confirmed that the proportion of long fibres had decreased compared to samples briefly exposed to the Gambles solution. This loss of mass and fibre shortening was accompanied by a loss of pathogenicity when injected into the peritoneal cavities of C57Bl/6 mice compared to fibres incubated briefly. CNT_SWdid not elicit an inflammogenic effect in the peritoneal cavity assay used here.</p> <p>Conclusions</p> <p>These results support the view that carbon nanotubes are generally durable but may be subject to bio-modification in a sample-specific manner. They also suggest that pristine carbon nanotubes, either individually or in rope-like aggregates of sufficient length and aspect ratio, can induce asbestos-like responses in mice, but that the effect may be mitigated for certain types that are less durable in biological systems. Results indicate that durable carbon nanotubes that are either short or form tightly bundled aggregates with no isolated long fibres are less inflammogenic in fibre-specific assays.</p

The Far-Infrared Spectral Energy Distributions of X-ray-selected Active Galaxies

[Abridged] We present ISO far-infrared (IR) observations of 21 hard X-ray selected AGN from the HEAO-1 A2 sample. We compare the far-IR to X-ray spectral energy distributions (SEDs) of this sample with various radio and optically selected AGN samples. The hard-X-ray selected sample shows a wider range of optical/UV shapes extending to redder near-IR colors. The bluer objects are Seyfert 1s, while the redder AGN are mostly intermediate or type 2 Seyferts. This is consistent with a modified unification model in which the amount of obscuring material increases with viewing angle and may be clumpy. Such a scenario, already suggested by differing optical/near-IR spectroscopic and X-ray AGN classifications, allows for different amounts of obscuration of the continuum emission in different wavebands and of the broad emission line region which results in a mixture of behaviors for AGN with similar optical emission line classifications. The resulting limits on the column density of obscuring material through which we are viewing the redder AGN are 100 times lower than for the standard optically thick torus models. The resulting decrease in optical depth of the obscuring material allows the AGN to heat more dust at larger radial distances. We show that an AGN-heated, flared, dusty disk with mass 10^9 solar and size of few hundred pc is able to generate optical-far-IR SEDs which reproduce the wide range of SEDs present in our sample with no need for an additional starburst component to generate the long-wavelength, cooler part of the IR continuum.Comment: 40 pages, 14 figures, accepted for publication in Astrophysical Journal, V. 590, June 10, 200

Prognosis of Differentiated Thyroid Cancer in Relation to Serum Thyrotropin and Thyroglobulin Antibody Status at Time of Diagnosis

BACKGROUND: Serum thyrotropin (TSH) concentration and thyroid autoimmunity may be of prognostic importance in differentiated thyroid cancer (DTC). Preoperative serum TSH level has been associated with higher DTC stage in cross-sectional studies; data are contradictory on the significance of thyroid autoimmunity at the time of diagnosis. OBJECTIVE: We sought to assess whether preoperative serum TSH and perioperative antithyroglobulin antibodies (TgAb) were associated with thyroid cancer stage and outcome in DTC patients followed by the National Thyroid Cancer Treatment Cooperative Study, a large multicenter thyroid cancer registry. METHODS: Patients registered after 1996 with available preoperative serum TSH (n=617; the TSH cohort) or perioperative TgAb status (n=1770; the TgAb cohort) were analyzed for tumor stage, persistent disease, recurrence, and overall survival (OS; median follow-up, 5.5 years). Parametric tests assessed log-transformed TSH, and categorical variables were tested with chi square. Disease-free survival (DFS) and OS was assessed with Cox models. RESULTS: Geometric mean serum TSH levels were higher in patients with higher-stage disease (Stage III/IV=1.48 vs. 1.02 mU/L for Stages I/II; p=0.006). The relationship persisted in those aged ≥45 years after adjusting for sex (p=0.01). Gross extrathyroidal extension (p=0.03) and presence of cervical lymph node metastases (p=0.003) were also significantly associated with higher serum TSH. Disease recurrence and all-cause mortality occurred in 37 and 38 TSH cohort patients respectively, which limited the power for survival analysis. Positive TgAb was associated with lower stage on univariate analysis (positive TgAb in 23.4% vs. 17.8% of Stage I/II vs. III/IV patients, respectively; p=0.01), although the relationship lost significance when adjusting for age and sex (p=0.34). Perioperative TgAb was not an independent predictor of DFS (hazard ratio=1.12 [95% confidence interval=0.74-1.69]) or OS (hazard ratio=0.98 [95% confidence interval=0.56-1.72]). CONCLUSIONS: Preoperative serum TSH level is associated with higher DTC stage, gross extrathyroidal extension, and neck node metastases. Perioperative TgAb is not an independent predictor of DTC prognosis. A larger cohort is required to assess whether preoperative serum TSH level predicts recurrence or mortality

Effects of High-Volume Versus High-Load Resistance Training on Skeletal Muscle Growth and Molecular Adaptations

We evaluated the effects of higher-load (HL) versus (lower-load) higher-volume (HV) resistance training on skeletal muscle hypertrophy, strength, and muscle-level molecular adaptations. Trained men (n = 15, age: 23 ± 3 years; training experience: 7 ± 3 years) performed unilateral lower-body training for 6 weeks (3× weekly), where single legs were randomly assigned to HV and HL paradigms. Vastus lateralis (VL) biopsies were obtained prior to study initiation (PRE) as well as 3 days (POST) and 10 days following the last training bout (POSTPR). Body composition and strength tests were performed at each testing session, and biochemical assays were performed on muscle tissue after study completion. Two-way within-subject repeated measures ANOVAs were performed on most dependent variables, and tracer data were compared using dependent samples t-tests. A significant interaction existed for VL muscle cross-sectional area (assessed via magnetic resonance imaging; interaction p = 0.046), where HV increased this metric from PRE to POST (+3.2%, p = 0.018) whereas HL training did not (−0.1%, p = 0.475). Additionally, HL increased leg extensor strength more so than HV training (interaction p = 0.032; HV \u3c HL at POST and POSTPR, p \u3c 0.025 for each). Six-week integrated non-myofibrillar protein synthesis (iNon-MyoPS) rates were also higher in the HV versus HL condition, while no difference between conditions existed for iMyoPS rates. No interactions existed for other strength, VL morphology variables, or the relative abundances of major muscle proteins. Compared to HL training, 6 weeks of HV training in previously trained men optimizes VL hypertrophy in lieu of enhanced iNon-MyoPS rates, and this warrants future research

Research Priorities for Achieving Healthy Marine Ecosystems and Human Communities in a Changing Climate

ABSTRACT: The health of coastal human communities and marine ecosystems are at risk from a host of anthropogenic stressors, in particular, climate change. Because ecological health and human well-being are inextricably connected, effective and positive responses to current risks require multidisciplinary solutions. Yet, the complexity of coupled social-ecological systems has left many potential solutions unidentified or insufficiently explored. The urgent need to achieve positive social and ecological outcomes across local and global scales necessitates rapid and targeted multidisciplinary research to identify solutions that have the greatest chance of promoting benefits for both people and nature. To address these challenges, we conducted a forecasting exercise with a diverse, multidisciplinary team to identify priority research questions needed to promote sustainable and just marine social-ecological systems now and into the future, within the context of climate change and population growth. In contrast to the traditional reactive cycle of science and management, we aimed to generate questions that focus on what we need to know, before we need to know it. Participants were presented with the question, "If we were managing oceans in 2050 and looking back, what research, primary or synthetic, would wish we had invested in today?" We first identified major social and ecological events over the past 60 years that shaped current human relationships with coasts and oceans. We then used a modified Delphi approach to identify nine priority research areas and 46 questions focused on increasing sustainability and well-being in marine social-ecological systems. The research areas we identified include relationships between ecological and human health, access to resources, equity, governance, economics, resilience, and technology. Most questions require increased collaboration across traditionally distinct disciplines and sectors for successful study and implementation. By identifying these questions, we hope to facilitate the discourse, research, and policies needed to rapidly promote healthy marine ecosystems and the human communities that depend upon them

UBVRI Light Curves of 44 Type Ia Supernovae

We present UBVRI photometry of 44 type-Ia supernovae (SN Ia) observed from 1997 to 2001 as part of a continuing monitoring campaign at the Fred Lawrence Whipple Observatory of the Harvard-Smithsonian Center for Astrophysics. The data set comprises 2190 observations and is the largest homogeneously observed and reduced sample of SN Ia to date, nearly doubling the number of well-observed, nearby SN Ia with published multicolor CCD light curves. The large sample of U-band photometry is a unique addition, with important connections to SN Ia observed at high redshift. The decline rate of SN Ia U-band light curves correlates well with the decline rate in other bands, as does the U-B color at maximum light. However, the U-band peak magnitudes show an increased dispersion relative to other bands even after accounting for extinction and decline rate, amounting to an additional ~40% intrinsic scatter compared to B-band.Comment: 84 authors, 71 pages, 51 tables, 10 figures. Accepted for publication in the Astronomical Journal. Version with high-res figures and electronic data at http://astron.berkeley.edu/~saurabh/cfa2snIa