Uncertainty in health risk analysis

This paper discuss several quantitative issues that arise in the analysis of health risks, beginning with principles such as de minimis and zero-risk. The paper also provides a probabilistic definition of risk in terms of hazard, context, consequence, magnitude, and uncertainty. The example relies on this definition to investigate, through sensitivity analysis, the effect that uncertainty has on the results obtained. The results, from a case study based on waterborne total arsenic, show that the choice of dose—response functions causes more uncertainty than any other component of risk analysis. Chemical carcinogenesis provides the basis for discussing inability to know as well as uncertainty. The conclusion is that risk analysis keeps uncertainty and inability to know separate; through this function, it provides a much needed method to present information to decision makers and the public.     

An implementation of storage management in capability environments

The exploitation of the salient features of capability-based addressing environments leads to a high number of small objects existing in memory at the same time. It is thus necessary to enhance the efficiency of the mechanisms for object relocation, and to avoid congestion of input/output devices due to swapping. In this paper, we present an approach to the management of a large virtual memory space aimed at solving these problems. We insert partial information concerning the physical allocation of each object into the virtual identifier of this object. Objects are grouped into large swapping units, called pages. The page size is independent of the average object size. This results in enhanced efficiency in managing the relocation information both with regard to memory requirements and access times. The allocation of objects into pages, and the movement of pages through the memory hierarchy, are controlled by user processes. This means that programs which have knowledge of their own use of virtual memory can increase their locality of reference, diminish the number of swap operations and reduce fragmentation.     

Reduced skin tumor development in cyclin D1-deficient mice highlights the oncogenic ras pathway in vivo

Cyclin D1 is part of a cell cycle control node consistently deregulated in most human cancers. However, studies with cyclin D1-null mice indicate that it is dispensable for normal mouse development as well as cell growth in culture. Here, we provide evidence that ras-mediated tumorigenesis depends on signaling pathways that act preferentially through cyclin D1. Cyclin D1 expression and the activity of its associated kinase are up-regulated in keratinocytes in response to oncogenic ras. Furthermore, cyclin D1 deficiency results in up to an 80% decrease in the development of squamous tumors generated through either grafting of retroviral ras-transduced keratinocytes, phorbol ester treatment of ras transgenic mice, or two-stage carcinogenesis.     

Transporting Deformations of Face Emotions in the Shape Spaces: A Comparison of Different Approaches

Studying the changes of shape is a common concern in many scientific fields. We address here two problems: (1) quantifying the deformation between two given shapes and (2) transporting this deformation to morph a third shape. These operations can be done with or without point correspondence, depending on the availability of a surface matching algorithm, and on the type of mathematical procedure adopted. In computer vision, the re-targeting of emotions mapped on faces is a common application. We contrast here four different methods used for transporting the deformation toward a target once it was estimated upon the matching of two shapes. These methods come from very different fields such as computational anatomy, computer vision and biology. We used the large diffeomorphic deformation metric mapping and thin plate spline, in order to estimate deformations in a deformational trajectory of a human face experiencing different emotions. Then we use naive transport (NT), linear shift (LS), direct transport (DT) and fanning scheme (FS) to transport the estimated deformations toward four alien faces constituted by 240 homologous points and identifying a triangulation structure of 416 triangles. We used both local and global criteria for evaluating the performance of the 4 methods, e.g., the maintenance of the original deformation. We found DT, LS and FS very effective in recovering the original deformation while NT fails under several aspects in transporting the shape change. As the best method may differ depending on the application, we recommend carefully testing different methods in order to choose the best one for any specific application.

     

Flow-based local optimization for image-to-geometry projection

The projection of a photographic data set on a 3D model is a robust and widely applicable way to acquire appearance information of an object. The first step of this procedure is the alignment of the images on the 3D model. While any reconstruction pipeline aims at avoiding misregistration by improving camera calibrations and geometry, in practice a perfect alignment cannot always be reached. Depending on the way multiple camera images are fused on the object surface, remaining misregistrations show up either as ghosting or as discontinuities at transitions from one camera view to another. In this paper we propose a method, based on the computation of Optical Flow between overlapping images, to correct the local misalignment by determining the necessary displacement. The goal is to correct the symptoms of misregistration, instead of searching for a globally consistent mapping, which might not exist. The method scales up well with the size of the data set (both photographic and geometric) and is quite independent of the characteristics of the 3D model (topology cleanliness, parametrization, density). The method is robust and can handle real world cases that have different characteristics: low level geometric details and images that lack enough features for global optimization or manual methods. It can be applied to different mapping strategies, such as texture or per-vertex attribute encoding.     

Steel-to-concrete bond after concrete splitting: test results

The definite trend towards the use of large-diameter rebars and the introduction of high-strength steels (f _y=500 to 600 MPa) make it necessary to study the effects of longitudinal splitting on the steel-to-concrete bond. The study of splitting effects requires firstly basic tests to be performed in order to gather experimental information on bond and confinement stresses acting at the bar-to-concrete interface. For this purpose, three series of tests were recently carried out at the Politecnico di Milano. The results make it possible to ascertain a few basic properties of the bond after concrete splitting, and to formulate empirical constitutive laws regarding the stresses and the displacements (bar slip and opening of the splitting crack). All specimens consisted of a short deformed bar embedded in a concrete block, which had a preformed splitting crack in the plane passing through the bar axis: twelve specimens (Tests A and C) were fitted up with a round deformed bar having crescent-shaped lugs (D_b=18 mm); seven specimens (Tests B) were fitted up with a specially machined deformed bar having a rectangular cross-section and straigth, lugs, so that concrete deterioration close to the bar could be investigated at the surface of the specimen, by means of the moiré technique. The tests were carried out at constant slip rate, up to very large slip values ( ); both the ascending and the descending branches of the stress-slip curves were measured, for four different values of the opening of the splitting crack. The agreement among the results of the three series is generally satisfactory and often very good: consequently, constitutive laws regarding the four main variables (crack opening and bar slip, shear and confinement stresses) can be worked out, as will be shown in a companion paper on constitutive relationships and on concrete deterioration at the bar-to-concrete interface.     

Complementary Effects of Carbamylated and Citrullinated LL37 in Autoimmunity and Inflammation in Systemic Lupus Erythematosus

LL37 acts as T-cell/B-cell autoantigen in Systemic lupus erythematosus (SLE) and psoriatic disease. Moreover, when bound to “self” nucleic acids, LL37 acts as “danger signal,” leading to type I interferon (IFN-I)/pro-inflammatory factors production. T-cell epitopes derived from citrullinated-LL37 act as better antigens than unmodified LL37 epitopes in SLE, at least in selected HLA-backgrounds, included the SLE-associated HLA-DRB1*1501/HLA-DRB5*0101 backgrounds. Remarkably, while “fully-citrullinated” LL37 acts as better T-cell-stimulator, it loses DNA-binding ability and the associated “adjuvant-like” properties. Since LL37 undergoes a further irreversible post-translational modification, carbamylation and antibodies to carbamylated self-proteins other than LL37 are present in SLE, here we addressed the involvement of carbamylated-LL37 in autoimmunity and inflammation in SLE. We detected carbamylated-LL37 in SLE-affected tissues. Most importantly, carbamylated-LL37-specific antibodies and CD4 T-cells circulate in SLE and both correlate with disease activity. In contrast to “fully citrullinated-LL37,” “fully carbamylated-LL37” maintains both innate and adaptive immune-cells’ stimulatory abilities: in complex with DNA, carbamylated-LL37 stimulates plasmacytoid dendritic cell IFN-α production and B-cell maturation into plasma cells. Thus, we report a further example of how different post-translational modifications of a self-antigen exert complementary effects that sustain autoimmunity and inflammation, respectively. These data also show that T/B-cell responses to carbamylated-LL37 represent novel SLE disease biomarkers.