Methods and tools for supporting industrial design innovation

The introduction of information technology (IT) systems to support designers’ activities and data management have profoundly affected company structure and design organization. This evolution has brought the introduction of systematic methods, close to information tools skills and prerogatives, using computer management and data recovery skills as main design support. The use of the IT also improved information exchange among different work figures involved during product development process. In this direction authors have intended to analyze the role and the implementation of systematic methods and tools within industrial designer area of the design process and their impact on the conceptual design phase in particular. Consequently, the research has been developed primarily in reference to design methods able to support the strict ideation stage of the Conceptual Design, that can be referred to two typologies: knowledge based and functional approaches. Subsequently authors have analyzed the information tools currently used during design process, as CAD systems, and some innovative, as Virtual and Augmented Reality tools, that can be used within industrial design area. The result of the study has been a formalization of the course followed during idea conceptual phase in order to include and to arrange the design methods and tools analysed. The research proposes a structured view of a process of product conceptualization, usually considered as mainly heuristic, focusing on the integration of methods and tools to support project and its communication. In this area the research has highlighted industrial designer role characteristics during design process, changeable in reference of project development level, and also some important new questions have been identified about the interaction between industrial designers and the other design areas involved in the process. In this direction the study has highlighted the need to support knowledge exchange and recovery, introducing the possibility to extend the research to the whole process and integrate industrial design and engineering collaboration in a more effective way. Keywords: Conceptual design process, Systematic innovation, Knowledge management, Integration</p

Telomere shortening as genetic risk factor of liver cirrhosis

Cirrhosis is the main complication of chronic liver disease, leads to progressive liver function impairment and is the main risk factor for the development of liver cancer. Liver failure at endstage cirrhosis is associated with increased mortality with liver transplantation as the only possible treatment at this stage. The pathogenesis of liver cirrhosis is not completely elucidated. Although the common factors leading to liver injury, such as viral hepatitis, alcohol consume or fatty liver disease can be identified in the majority of patients a small percentage of patients have no apparent risk factors. Moreover given the same risk factors, some patients progress to cirrhosis whereas others have a benign course, the reason remains unclear. In order to develop new diagnostic and therapeutic tools, it is s essential to understand the pathogenesis of cirrhosis. The identification of genetic risk factors associated with cirrhosis is one of the possible approach to achieve these goal. In the past years several studies have supported the role of telomere shortening and cirrhosis. In the recent year several studies on the relation between several single nucleotide polymorphism (SNPs) and cirrhosis have been published; it has been proposed also a cirrhosis risk score based on seven SNPs. Also epidemiological studies on identical twins and in different ethnic groups have been supporting the importance of the role of genetic risk factors. Finally in the very recent years it has been suggested that telomere shortening may represent a genetic risk factor for the development of cirrhosis

Telomeres and atherosclerosis

Abstract The pathogenesis of atherosclerosis, an age-related disorder, may be due to a premature biological ageing. Cellular senescence, the finite replicative lifespan of cells, plays a critical role in the pathogenesis of atherosclerosis. The biological mechanism that triggers the onset of cellular senescence is thought to be telomere shortening. The two major mechanisms responsible for telomere shortening are the end-replication problem, oxidative DNA damage as well as inflammation induced by environmental risk factors. Repair of the endothelium depends on the presence of endothelial progenitor cells which depends on the hematopoietic stem cells (HSC) reserves. In numerous past studies, short LTL has been associated with atherosclerosis. Here we review the literature on telomere biology and coronary artery disease (CAD)

The Dynamic Regulation of Intestinal Stem Cells by Notch Signaling.

The intestinal epithelium has one of the fastest cellular turnover rates in the body, a process fueled by a highly active intestinal stem cell (ISC) compartment. Two ISC populations are thought to exist: the active crypt base columnar stem cell (CBCC) and quiescent stem cells (QSCs). The Notch signaling pathway is one of several pathways known to regulate ISC function. My thesis work has focused on understanding the specificity and kinetics underlying Notch regulation of CBCCs. First, I probed the specificity of Notch receptors in regulating intestinal homeostasis by conditionally deleting Notch1 (N1) and/or Notch2 (N2) in the intestinal epithelium in genetic mouse models. Deletion of N1 but not N2 led to increased numbers of secretory cells, demonstrating that N1 is the dominant receptor regulating cell fate decisions. Additionally, N1 deletion reduced the CBCC population by 50% and eliminated recovery after irradiation, discoveries that have clinical implications for using targeted anti-Notch drugs as cancer treatments. My thesis also investigated the cellular mechanism of decreased CBCCs and decreased transit-amplifying (TA) cell proliferation after Notch inhibition. I tracked the consequences of acute Notch inhibition on stem cells over time. Surprisingly, while acute inhibition resulted in decreased CBCC number it also led to increased TA proliferation rather than the decreased proliferation previously observed with chronic inhibition. I devised a compartmental mathematical model of the intestinal crypt to reconcile the proliferation differences observed with acute and chronic Notch inhibition. The model favored a mechanism where Notch signaling regulates both the symmetry of CBCC division into TA cells, as well as repopulation of the CBCC compartment, presumably by activation of QSCs. Further work investigating the role of Notch in QSCs suggests that Notch regulation of CBCC replacement is through regulation of the CBCC niche rather than direct regulation of QSCs. In summary, my thesis work has probed the role of Notch in intestinal epithelial homeostasis and CBCC maintenance. I show that loss of Notch signaling leads to a dynamic shift of CBCCs into the TA cell compartment and that N1 is the key receptor regulating these changes.PHDMolecular and Integrative PhysiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/120757/1/acarulli_1.pd

Telomere and telomerase in chronic liver disease and hepatocarcinoma

The pathogenesis of liver cirrhosis is not completely elucidated. Although in the majority of patients, the risk factors may be identified in B and C viral hepatitis, alcohol intake, drugs or fatty liver disease, there is a small percentage of patients with no apparent risk factors. In addition, the evolution of chronic liver disease is highly heterogeneous from one patient to another. Among patient with identical risk factors, some rapidly progress to cirrhosis and hepatocellular carcinoma (HCC) whereas others have a benign course. Therefore, a genetic predisposition may contribute to the development of cirrhosis and HCC. Evidence supporting the role of genetic factors as a risk for cirrhosis has been accumulating during the past years. In addition to the results from epidemiological studies, polymorphisms studies and data on twins, the concept of telomere shortening as a genetic risk factor for chronic liver disease and HCC has been proposed. Here we review the literature on telomerase mutations, telomere shortening and liver disease including hepatocellular carcinoma

Bleeding jejunal varices and portal thrombosis in a splenectomized patient with hereditary spherocytosis

Bleeding from varices located in the small bowel is a very uncommon finding; nonetheless, such events accompany with a high mortality rate (1– 4). Moreover, early diagnosis of jejunal or ileal varices cannot usually be accomplished with standard diagnostic tools (ie, esophagogastroduodenoscopy, colonoscopy). Most reports in the literature relate to subjects with liver cirrhosis, often with hepatocarcinoma; in unusual anatomical situations, varices may develop beyond the ligament of Treitz in adjunct to the far more common location in the esophageal and gastric wall. Thrombosis of the portal vein is a common feature in such conditions. Portal thrombosis has also been described in association with overt or latent myeloproliferative diseases (5); its occurrence in nonneoplastic hematological conditions in subjects with normal liver function is quite uncommon. This report describes the observation of jejunal varices, with repeated episodes of “melena of unknown origin,” some of which quite severe, as their clinical presentation in a patient with portal thrombosis and with otherwise absolutely normal liver function, who had undergone splenectomy for hereditary spherocytosis in early adolescence