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The embodiment design phase consists of rough selections/arrangements of materials, technologies used, dimensions, and main components. During this phase, many behavior models are used to verify the achievement of design objectives. The lack of confidence in these models due to the assumptions adopted causes designers to realize many prototypes during product development, causing time/cost-consuming loops of the "trial-and-error" procedure. We propose a decision model that integrates the accuracy of behavior models into decision-making. The objective is to limit the use of physical prototypes and improve the quality of decision-making. Each design alternative is evaluated using two indicators. The first is a desirability indicator that measures the level of completion of design objectives. The second indicator assesses the risk associated with the accuracy of behavior models using AHP, FMEA, and experimental tests on a prototype. The proposed approach was applied to the development of a solar collector.

Product design is a creative and multidisciplinary activity that often necessitates the application of analytical and innovative support tools to enhance the concept research phase and solutions development. The TRIZ theory, a highly effective innovation method, has demonstrated its efficacy in supporting innovation across various fields. In this context, our focus has been on integrating TRIZ into the product design process involving engineering designers. This article provides a descriptive and critically assessed evaluation of the operational impact of TRIZ on the design activity, specifically in the development of a "Wastewater Screening and Filtration System" during the preliminary design phases. The objective of this research is to assess the influence of TRIZ utilization on the engineering designers' ability to address a design problem. The ultimate goal is to establish an innovative design support approach based on the use of TRIZ tools that is easily comprehensible and applicable to future designers. Within this article, we present both quantitative and qualitative results of the exploitation of TRIZ tools combined with an energy analysis of the requirement in the product design field.

An integrated temporal study of a long-term ecological research and monitoring database of the St. Lawrence River was carried out. A long and mostly uninterrupted high temporal resolution record of fluorometric data from 2014 to 2018 was used to examine phytoplankton fluorometric variables at several scales and to identify temporal patterns and their main environmental drivers. Sets of temporal eigenvectors were used as modulating variables in a multiscale codependence analysis to relate the fluorometric variables and various environmental variables at different temporal scales. Fluorometric patterns of phytoplankton biomass in the St. Lawrence River are characterized by large, yearly-scale patterns driven by seasonal changes in water temperature, and to a lesser extent water discharge, over which finer-scale temporal patterns related to colored dissolved organic matter and weather variables can be discerned at shorter time scales. The results suggest that such an approach to characterize phytoplankton biomass in large rivers may be useful for processing large data sets from remote sensing efforts for detecting subtle large-scale changes in water quality due to land use practices and climate change.

Abstract Monitoring select ecosystem variables across time and interpreting the collected data are essential components of ecosystem assessment supporting management. Increasingly affordable sensors and computational capacity have made very large dataset assembly more common. However, these datasets initiate analytical challenges by their size and theoretical challenges due to the scale of the processes they encompass. Multiscale assessment of high temporal resolution water quality sensor data (temperature, in vivo chlorophyll a, colored dissolved organic matter) collected year‐round was conducted for the Upper St. Lawrence River. Using numerical methods that directly integrate the concept of scale, we show that consideration of scale‐dependent processes can lead to increased predictive power and a clearer understanding of ecosystem function. These results suggest that multiscale methods are not only an alternative way of approaching long‐term data assessment, but also a necessity in order to avoid spurious interpretation. Consequently, the concept of scale as described here can be consistently integrated into long‐term data studies to assist in the interpretation of high‐resolution data that help describe natural phenomena in aquatic systems.

The stability constants of binary complexes of 2,4-dichlorophenoxyacetic acid (2,4-D), 4-chloro-2- methylphenoxy)acetic acid (2,4-MCPA) and (4-chloro-2-methylphenoxy) propionic acid (2,4-MCPP) with Hg(ll), Pb(ll) have been calculated at 298K and at ionic strength µ=0.1 (NaNO3). Potentiometric measurements display two hydroxide complexes for Hg(ll): HgH-1A and HgH-2A2 whereas for Pb(ll) we observe the formation of three species PbH-1A, PbH-1A2 and PbH-2A2. With regard to the successive complexes, no other system represents this type of complexes under our experimental conditions. The order of capacity of complexation compared to metal for the three ligands is Hg(ll)>Pb(ll). Finally, the study in solution has been completed by a quantum examination of the structures of the complex of Hg(ll) by the AM1 method. [ABSTRACT FROM AUTHOR]

We previously identified the aberrantly expressed cell cycle regulator cyclin B1 as a tumor antigen recognized by antibodies and T cells from patients with breast, lung, and head and neck cancers. Ordinarily expressed only transiently in the G2/M stage of the cell cycle in normal cells, cyclin B1 is constitutively expressed at high levels in the cytoplasm of these and many other tumor types, leading to its recognition by the cancer patient's immune system. We report here an unexpected observation that cyclin B1-specific antibody and memory CD4 and CD8 T cells are also found in many healthy individuals who have no history of cancer. Moreover, young as well as older healthy people have these responses suggesting that events other than cancer, which occur either early in life or throughout life, may lead to aberrant cyclin B1 expression and anti-cyclin B1 immunity. The role, if any, of immunity to this tumor-associated antigen is not known. We wanted to determine specifically whether immunity to cyclin B1 might be important in the immunosurveillance of cyclin B1+ tumors. We therefore tested in mice the effectiveness of vaccine-elicited anti-cyclin B1 immunity against a cyclin B1+ mouse tumor that was chosen based on our published observation that cyclin B1 overexpression is associated with the lack of p53 function. We found that cyclin B1 DNA prime-protein boost vaccine protected mice from a challenge with a tumor cell line that was established from a tumor arising in the p53(-/-) mouse that spontaneously overexpresses cyclin B1.

Primary hydatid cyst of the parotid gland is still an exceptional localization. The parotid gland is an uncommon site, even in our country, in which echinococcal disease is endemic. We report six cases of primary hydatid cyst of the parotid gland who presented with an isolated mass. The diagnosis was based on ultrasonography, which showed a parotid gland cystic mass. The echinococcal immunologic test (enzyme-linked immunosorbent assay) was positive in two cases. The surgical treatment consisted of total resection of the cyst, without rupture of the cystic wall and preserving the gland, in four cases and resection of the prominent dome in two cases. The diagnosis was confirmed on macroscopic examination of the resected pieces. In all cases, the postoperative course was uneventful. There was no recurrence at the 17-month follow-up.

Intradermal (i.d.) immunization is a promising route of vaccine administration. Suitable i.d. adjuvants are important to increase vaccine efficacy in poorly responding populations such as the elderly or for dose-sparing strategies in the face of vaccine shortages. Bacterial exotoxins, such as Escherichia coli heat-labile enterotoxin (LT), exert strong immunostimulatory effects through binding to monosialoganglioside (GM1) cell surface receptors; however, injection is hampered by local inflammation. We demonstrate that the injection of LT formulations deficient in GM1 binding by mutation (LT(G33D)) or in vitro ligand coupling does not cause localized edema and inflammation in mice, yet these formulations retain potent adjuvant activity by enhancing functional Ab and cellular immune responses to coadministered Ags. Complete protection against in vivo lethal tetanus toxin challenge and the induction of Ag-specific CTL responses capable of killing target cells in vivo indicated in vivo efficacy of the induced immune responses. LT(G33D) proved superior to standard alum adjuvant regarding the magnitude and breadth of the induced immune responses. Immunizations in complex ganglioside knockout mice revealed a GM1-independent pathway of LT adjuvanticity. Immunostimulation by i.d. LT(G33D) is explained by its ability to induce migration of activated APCs to the proximal draining lymph nodes. LT(G33D) is a promising candidate adjuvant for human trials of parenteral vaccines in general and for current i.d. vaccine development in particular.

Based on the tolerogenic properties of IgG carriers and B cell Ag presentation, we developed a retrovirally mediated gene expression approach for treatment of autoimmune conditions. In this study, we show that the IgG-Ag retroviral constructs, expressing myelin basic protein (MBP) or glutamic acid decarboxylase in B cells, can be used for the treatment of murine models for multiple sclerosis and diabetes. Transduction of syngeneic B cells with MBP-IgG leads to the amelioration of ongoing experimental allergic encephalomyelitis induced by the transfer of primed cells from PLxSJL F(1) mice with ongoing disease and could be effective even after symptoms appeared. This effect is specific and does not involve bystander suppression because treatment with MBP-IgG does not affect disease induced after immunization with proteolipid protein immunodominant peptide plus MBP. Interestingly, if donor B cells are derived from gld mice (Fas ligand-negative), then tolerance is not induced with a model Ag although there was no evidence for Fas ligand-mediated deletion of target T cells. In spontaneous diabetes in nonobese diabetic mice, we were able to stop the ongoing autoimmune process by treatment at 7-10 wk with glutamic acid decarboxylase-IgG retrovirally transduced B cells, or attenuate it with B cells transduced with an insulin B chain (B9-23) epitope IgG fusion protein. Furthermore, IgG fusion protein gene therapy can also protect primed recipients from Ag-induced anaphylactic shock, and thus does not cause immune deviation. These results demonstrate proof of principle for future efforts to develop this approach in a clinical setting.

Tolerance induction would be an ideal way to treat autoimmune diseases, especially if achievable in primed individuals. Moreover, specific tolerance would preclude the need for immunosuppressive treatment with its side effects. In this review, we will revisit the historical concepts of tolerance, and introduce a novel approach to tolerance via gene therapy. Our model system is based on the tolerogenicity of IgG carriers and B-cell antigen presentation. Results with this model demonstrate that it is simple and effective even in primed recipients, and has proven efficacy in three autoimmune models. We discuss the mechanisms of tolerance with fusion IgG's and analyze how our model of gene therapy approached can be utilized to fit in the future treatment of autoimmune conditions.

A gene therapy model has been designed to induce tolerance to multiple epitopes expressed in-frame on a soluble IgG fusion protein scaffold. Tolerance to the lambda repressor cI sequence p1-102 or its immunodominant epitopes (p12-26, p73-88) can be elicited when bone marrow (BM) or LPS blasts are transduced and injected into naive or even primed recipients. To explore the mechanism of tolerance, class II(-/-) (knockout, KO) BM cells were transduced with p1-102-IgG and transferred to irradiated recipients. These cells failed to induce tolerance to challenge with p1-102 epitopes, whereas transduced +/+ BM cells did. This supports the importance of class II MHC on the tolerogenic APC rather than secretion and representation in tolerogenesis. When BM cells from muMT KO mice were transfected with p12-26-IgG and injected into irradiated mice, these transduced BM cells also failed to induce tolerance to an immunodominant epitope. These results suggest the direct involvement of B cells in tolerance to p1-102 epitopes. IL-10 KO BM cells infected with a p12-26-IgG construct were still tolerogenic. Importantly, anti-CTLA-4 injections reversed tolerance in primed, but not in naive, recipients of transduced LPS blasts. These data emphasize the importance of MHC class II presentation, B cell involvement, and CTLA-4 engagement in induction and/or maintenance of tolerance.

IgG molecules can be highly tolerogenic carriers for associated antigens. Previously, we reported that recipients of bone marrow or lipopolysaccharide-stimulated B-cell blasts, both of which were retrovirally gene-transferred with an immunodominant peptide in-frame with the variable region of a murine IgG heavy chain, were rendered profoundly unresponsive to that epitope. To further investigate whether tolerance to larger molecules can be achieved via this approach and whether the IgG scaffold is important for induction and maintenance of immunological tolerance, we engineered two retroviral constructs encoding the cI lambda repressor (MBAE-1-102 and MBAE-1-102-IgG) for gene transfer. Our results show that recipients of bone marrow or peripheral B cells, transduced with the MBAE-1-102-IgG recombinant, are hyporesponsive to p1-102. In addition, the self-IgG scaffold enhanced the induction and maintenance of such an immune hyporesponsiveness. Thus, our studies demonstrate that in vivo-expressed IgG heavy chain fusion protein can be processed and presented on the appropriate MHC class II, resulting in hyporesponsiveness to that antigen and offering an additional therapeutic approach to autoimmune diseases.

The closed laryngeal traumas by attempt of hanging are rarely studied by medical imaging. The lesions are evaluated by fiberoptic endoscopy and CT scan. We report a case of complicated lesions of the larynx with rupture of the cricothyroid membrane, diagnosed by CT scan and we discuss the usefulness of this technique.

This study of acute leukaemia in adult at the two main hospitals in Dakar- the General Hospital from January 1980 to June 1986 and the A. Le Dantec Hospital from January 1978 to June 1986 - shows the progression of this ailment, which remains rare (0.85% of admissions - 5 cases per year). Certain clinical peculiarities are stressed (high frequency of infectious symptoms, considerable splenomegaly , adenopathy often present in acute myeloid leukaemia. More severe biological signs are evident than in series in the West, and (L.A.M.3) forms dominate. Grave developments are often the result of a shortage of diagnostic and therapeutic equipment. The authors stress the need to create a haematological clinic.