08221 Abstracts Collection -- Geometric Modeling

From May 26 to May 30 2008 the Dagstuhl Seminar 08221 ``Geometric Modeling\u27\u27 was held in the International Conference and Research Center (IBFI), Schloss Dagstuhl. During the seminar, several participants presented their current research, and ongoing work and open problems were discussed. Abstracts of the presentations given during the seminar as well as abstracts of seminar results and ideas are put together in this paper. The first section describes the seminar topics and goals in general. Links to extended abstracts or full papers are provided, if available

A voxel-based method of constructing and skinning conformal and functionally graded lattice structures suitable for additive manufacturing

Additive Manufacturing (AM) enables the production of geometrically complex parts that are difficult to manufacture by other means. However, conventional CAD systems are limited in the representation of such parts. This issue is exacerbated when lattice structures are combined or embedded within a complex geometry. This paper presents a computationally efficient, voxel-based method of generating lattices comprised of practically any cell type that can conform to an arbitrary external geometry. The method of conforming involves the tessellation and trimming of unit cells that can leave ‘hanging’ struts at the surface, which is a possible point of weakness in the structure. A method of joining these struts to form an external two dimensional lattice, termed a ‘net-skin’ is also described. Traditional methods of manufacturing lattice structures generally do not allow variation of cell properties within a structure; however, additive manufacturing enables graded lattices to be generated that are potentially more optimal. A method of functionally grading lattices is, therefore, also described to take advantage of this manufacturing capability

Seasonal changes in patterns of gene expression in avian song control brain regions.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Photoperiod and hormonal cues drive dramatic seasonal changes in structure and function of the avian song control system. Little is known, however, about the patterns of gene expression associated with seasonal changes. Here we address this issue by altering the hormonal and photoperiodic conditions in seasonally-breeding Gambel's white-crowned sparrows and extracting RNA from the telencephalic song control nuclei HVC and RA across multiple time points that capture different stages of growth and regression. We chose HVC and RA because while both nuclei change in volume across seasons, the cellular mechanisms underlying these changes differ. We thus hypothesized that different genes would be expressed between HVC and RA. We tested this by using the extracted RNA to perform a cDNA microarray hybridization developed by the SoNG initiative. We then validated these results using qRT-PCR. We found that 363 genes varied by more than 1.5 fold (>log(2) 0.585) in expression in HVC and/or RA. Supporting our hypothesis, only 59 of these 363 genes were found to vary in both nuclei, while 132 gene expression changes were HVC specific and 172 were RA specific. We then assigned many of these genes to functional categories relevant to the different mechanisms underlying seasonal change in HVC and RA, including neurogenesis, apoptosis, cell growth, dendrite arborization and axonal growth, angiogenesis, endocrinology, growth factors, and electrophysiology. This revealed categorical differences in the kinds of genes regulated in HVC and RA. These results show that different molecular programs underlie seasonal changes in HVC and RA, and that gene expression is time specific across different reproductive conditions. Our results provide insights into the complex molecular pathways that underlie adult neural plasticity

Opium use and risk of mortality from digestive diseases: A prospective cohort study

Objectives:Opium use, particularly in low doses, is a common practice among adults in northeastern Iran. We aimed to investigate the association between opium use and subsequent mortality from disorders of the digestive tract.Methods:We used data from the Golestan Cohort Study, a prospective cohort study in northeastern Iran, with detailed, validated data on opium use and several other exposures. A total of 50,045 adults were enrolled during a 4-year period (2004-2008) and followed annually until December 2012, with a follow-up success rate of 99. We used Cox proportional hazard regression models to evaluate the association between opium use and outcomes of interest.Results:In all, 8,487 (17) participants reported opium use, with a mean duration of 12.7 years. During the follow-up period 474 deaths from digestive diseases were reported (387 due to gastrointestinal cancers and 87 due to nonmalignant etiologies). Opium use was associated with an increased risk of death from any digestive disease (adjusted hazard ratio (HR)=1.55, 95 confidence interval (CI)=1.24-1.93). The association was dose dependent, with a HR of 2.21 (1.57-3.31) for the highest quintile of cumulative opium use vs. no use (P trend =0.037). The HRs (95 CI) for the associations between opium use and malignant and nonmalignant causes of digestive mortality were 1.38 (1.07-1.76) and 2.60 (1.57-4.31), respectively. Increased risks were seen both for smoking opium and for ingestion of opium.Conclusions:Long-term opium use, even in low doses, is associated with increased risk of death from both malignant and nonmalignant digestive diseases

Magnetic resonance imaging, magnetic resonance arthrography and ultrasonography for assessing rotator cuff tears in people with shoulder pain for whom surgery is being considered

Background Shoulder pain is a very common symptom. Disorders of the rotator cuff tendons due to wear or tear are among the most common causes of shoulder pain and disability. Magnetic resonance imaging (MRI), magnetic resonance arthrography (MRA) and ultrasound (US) are increasingly being used to assess the presence and size of rotator cuff tears to assist in planning surgical treatment. It is not known whether one imaging method is superior to any of the others.Objectives To compare the diagnostic test accuracy of MRI, MRA and US for detecting any rotator cuff tears (i.e. partial or full thickness) in people with suspected rotator cuff tears for whom surgery is being considered.Search methods We searched the Cochrane Register of Diagnostic Test Accuracy Studies, MEDLINE, EMBASE, and LILACS from inception to February 2011. We also searched trial registers, conference proceedings and reference lists of articles to identify additional studies. No language or publication restrictions were applied.Selection criteria We included all prospective diagnostic accuracy studies that assessed MRI, MRA or US against arthroscopy or open surgery as the reference standard, in people suspected of having a partial or full thickness rotator cuff tear. We excluded studies that selected a healthy control group, or participants who had been previously diagnosed with other specific causes of shoulder pain such as osteoarthritis or rheumatoid arthritis. Studies with an excessively long period (a year or longer) between the index and reference tests were also excluded.Data collection and analysis Two review authors independently extracted data on study characteristics and results of included studies, and performed quality assessment according to QUADAS criteria. Our unit of analysis was the shoulder. for each test, estimates of sensitivity and specificity from each study were plotted in ROC space and forest plots were constructed for visual examination of variation in test accuracy. Meta-analyses were performed using the bivariate model to produce summary estimates of sensitivity and specificity. We were unable to formally investigate potential sources of heterogeneity because of the small number of studies.Main results We included 20 studies of people with suspected rotator cuff tears (1147 shoulders), of which six evaluated MRI and US (252 shoulders), or MRA and US (127 shoulders) in the same people. Many studies had design flaws, with the potential for bias, thus limiting the reliability of their findings. Overall, the methodological quality of the studies was judged to be low or unclear. for each test, we observed considerable heterogeneity in study results, especially between studies that evaluated US for the detection of full thickness tears and studies that evaluated MRA for the detection of partial thickness tears. the criteria for a positive diagnostic test (index tests and reference standard) varied between studies.Meta-analyses were not possible for studies that assessed MRA for detection of any rotator cuff tears or partial thickness tears. We found no statistically significant differences in sensitivity or specificity between MRI and US for detecting any rotator cuff tears (P = 0.13), or for detecting partial thickness tears (P = 1.0). Similarly, for the comparison between MRI, MRA and US for detecting full thickness tears, there was no statistically significant difference in diagnostic performance (P = 0.7). for any rotator cuff tears, the summary sensitivity and specificity were 98% (95% CI 92% to 99%) and 79% (95% CI 68% to 87%) respectively for MRI (6 studies, 347 shoulders), and 91% (95% CI 83% to 95%) and 85% (95% CI 74% to 92%) respectively for US (13 studies, 854 shoulders). for full thickness tears, the summary sensitivity and specificity were 94% (95% CI 85% to 98%) and 93% (95% CI 83% to 97%) respectively for MRI (7 studies, 368 shoulders); 94% (95% CI 80% to 98%) and 92% (95% CI 83% to 97%) respectively for MRA (3 studies, 183 shoulders); and 92% (95% CI 82% to 96%) and 93% (95% CI 81% to 97%) respectively for US (10 studies, 729 shoulders).Because few studies were direct head-to-head comparisons, we could not perform meta-analyses restricted to these studies. the test comparisons for each of the three classifications of the target condition were therefore based on indirect comparisons which may be prone to bias due to confounding.Authors' conclusions MRI, MRA and US have good diagnostic accuracy and any of these tests could equally be used for detection of full thickness tears in people with shoulder pain for whom surgery is being considered. the diagnostic performance of MRI and US may be similar for detection of any rotator cuff tears. However, both MRI and US may have poor sensitivity for detecting partial thickness tears, and the sensitivity of US may be much lower than that of MRI. the strength of evidence for all test comparisons is limited because most studies were small, heterogeneous and methodologically flawed, and there were few comparative studies. Well designed studies that directly compare MRI, MRA and US for detection of rotator cuff tears are needed.Universidade Federal de São Paulo, BrazilParker Institute, DenmarkOak FoundationTeesside University, UKUniversidade Federal de São Paulo, Dept Orthopaed & Traumatol, BR-04038032 São Paulo, BrazilMonash Univ, Sch Publ Hlth & Prevent Med, Dept Epidemiol & Prevent Med, Monash Dept Clin Epidemiol,Cabrini Hosp, Malvern, AustraliaUniv Birmingham, Birmingham, W Midlands, EnglandUniv Teesside, Hlth & Social Care Inst, Middlesbrough, Cleveland, EnglandUniversidade Federal de São Paulo, Dept Orthopaed & Traumatol, BR-04038032 São Paulo, BrazilWeb of Scienc

Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways

The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived metabolite itaconate, enhances oncolytic virotherapy with VSVΔ51 in various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids and organotypic brain tumor slices. Furthermore, 4-OI in combination with VSVΔ51 improves therapeutic outcomes in a resistant murine colon tumor model. Mechanistically, we find that 4-OI suppresses antiviral immunity in cancer cells through the modification of cysteine residues in MAVS and IKKβ independently of the NRF2/KEAP1 axis. We propose that the combination of a metabolite-derived drug with an oncolytic virus agent can greatly improve anticancer therapeutic outcomes by direct interference with the type I IFN and NF-κB-mediated antiviral responses.</p

Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways

The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived metabolite itaconate, enhances oncolytic virotherapy with VSVΔ51 in various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids and organotypic brain tumor slices. Furthermore, 4-OI in combination with VSVΔ51 improves therapeutic outcomes in a resistant murine colon tumor model. Mechanistically, we find that 4-OI suppresses antiviral immunity in cancer cells through the modification of cysteine residues in MAVS and IKKβ independently of the NRF2/KEAP1 axis. We propose that the combination of a metabolite-derived drug with an oncolytic virus agent can greatly improve anticancer therapeutic outcomes by direct interference with the type I IFN and NF-κB-mediated antiviral responses.</p

Sonic Hedgehog Signaling in Limb Development.

The gene encoding the secreted protein Sonic hedgehog (Shh) is expressed in the polarizing region (or zone of polarizing activity), a small group of mesenchyme cells at the posterior margin of the vertebrate limb bud. Detailed analyses have revealed that Shh has the properties of the long sought after polarizing region morphogen that specifies positional values across the antero-posterior axis (e.g., thumb to little finger axis) of the limb. Shh has also been shown to control the width of the limb bud by stimulating mesenchyme cell proliferation and by regulating the antero-posterior length of the apical ectodermal ridge, the signaling region required for limb bud outgrowth and the laying down of structures along the proximo-distal axis (e.g., shoulder to digits axis) of the limb. It has been shown that Shh signaling can specify antero-posterior positional values in limb buds in both a concentration- (paracrine) and time-dependent (autocrine) fashion. Currently there are several models for how Shh specifies positional values over time in the limb buds of chick and mouse embryos and how this is integrated with growth. Extensive work has elucidated downstream transcriptional targets of Shh signaling. Nevertheless, it remains unclear how antero-posterior positional values are encoded and then interpreted to give the particular structure appropriate to that position, for example, the type of digit. A distant cis-regulatory enhancer controls limb-bud-specific expression of Shh and the discovery of increasing numbers of interacting transcription factors indicate complex spatiotemporal regulation. Altered Shh signaling is implicated in clinical conditions with congenital limb defects and in the evolution of the morphological diversity of vertebrate limbs