第9届意大利传感器及微系统会议会议录

本书是由意大利传感器及微系统学会（AISFM）组织的第9届意大利传感器及微系统会议的会议录。这次会议于2004年2月8—11日在意大利北部城市费拉拉举行。它是由费拉拉大学物理系主办的。整个会议被分成了11个口头宣读分组会和2个书面张贴分组会。这本会议录收录了来自103个研究单位的83篇论文，充分表明了意大利当前在该领域中进行着非常活跃的研究，     

Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy

Noonan and LEOPARD syndromes are developmental disorders with overlapping features, including cardiac abnormalities, short stature and facial dysmorphia. Increased RAS signaling owing to PTPN11, SOS1 and KRAS mutations causes approximately 60% of Noonan syndrome cases, and PTPN11 mutations cause 90% of LEOPARD syndrome cases. Here, we report that 18 of 231 individuals with Noonan syndrome without known mutations (corresponding to 3% of all affected individuals) and two of six individuals with LEOPARD syndrome without PTPN11 mutations have missense mutations in RAF1, which encodes a serine-threonine kinase that activates MEK1 and MEK2. Most mutations altered a motif flanking Ser259, a residue critical for autoinhibition of RAF1 through 14-3-3 binding. Of 19 subjects with a RAF1 mutation in two hotspots, 18 (or 95%) showed hypertrophic cardiomyopathy (HCM), compared with the 18% prevalence of HCM among individuals with Noonan syndrome in general. Ectopically expressed RAF1 mutants from the two HCM hotspots had increased kinase activity and enhanced ERK activation, whereas non-HCM-associated mutants were kinase impaired. Our findings further implicate increased RAS signaling in pathological cardiomyocyte hypertrophy.     

Systemic View of Interorganisational Relationships: An Analysis of Business Networks

Business networks are formed by organisations with common interests. Inter-firm relations can bring to the companies involved an important contribution in the innovation processes: stimulating the division and sharing of scientific and technical information. This union between companies seems to be an appropriate alternative to promote the organisation's effectiveness. Considering the relevance of inter-organisation networks, their consolidation and the need to understand their essence as a mechanism of competitive advantage, this study is a theoretical reflection on the development of business networks and their proliferation. Using multiple perspectives, the paper discusses the classic authors, as well as contemporary references. It also analyzes the concept of networks and their importance, from a system's perspective.The systemic analysis emphasizes a holistic interpretation, considers the environment, the interdependence of the parts and the business inter-organisation actions. More than a theory, the systemic view can be understood as a model of empirical analysis, used to better understand complex phenomena. Considering inter-organisational relations, the systemic approach consists of the mechanism to understand the dynamics of business networks, their interface, especially considering their role in gaining a competitive advantage. The results discussed in this paper can bring a rich understanding of the role of networks for companies that participate in this initiative.Flávia was sponsored in her Ph.D by CAPES, a Foundation subordinated to the Ministry of Education of Brazil.     

Using Soft Systems Methodology to Fight Against Info-Exclusion: The Experience of a Brazilian University

The aim of this paper is to apply a systemic methodology to analyse the concept of info-inclusion which can guide strategic actions of institutions within civil society and within several levels of government. The paper provides a plan of action that, integrated with other tools, aims at fighting the technological and social gap. We apply Soft System Methodology (SSM), because it provides a holistic approach to info-exclusion. SSM is often used to analyse and resolve problems in complex social studies such as info-exclusion. An info-exclusion reduction project, developed by a university in the country region of Sao Paulo will be provided as a case study. This project is one of the several Brazilian initiatives to solve the problem of limited access to information technology tools. We start by contextualising info-exclusion in Brazil and follow with a review of SSM. We then introduce the concept of info-inclusion and apply SSM to it. We end with a discussion of the results obtained and with some suggestions for action and possible improvements.     

Systemic Model for Diagnosis of the Micro,Small and Medium Enterprises from Two Cities from the Countryside of the State of <Emphasis Type="Italic">São Paulo</Emphasis> in Brazil

This article presents a proposal of a systemic model composed for the micro and small companies (MSE) of the region of Ribeirão Preto and the agents which influenced their environment. The proposed model was based on Stafford Beer’s (Diagnosing the system for organizations. Chichester, Wiley, 1985) systemic methodologies VSM (Viable System Model) and on Werner Ulrich’s (1983) CSH (Critical Systems Heuristics). The VSM is a model for the diagnosis of the structure of an organization and of its flows of information through the application of the cybernetics concepts (Narvarte, In El Modelo del Sistema Viable—MSV: experiencias de su aplicación en Chile. Proyecto Cerebro Colectivo del IAS, Santiago, 2001). On the other hand, CSH focus on the context of the social group applied to the systemic vision as a counterpoint to the organizational management view considered by the VSM. MSE of Ribeirão Preto and Sertãozinho had been analyzed as organizations inserted in systems that relate and integrate with other systems concerning the public administration, entities of representation and promotion agencies. The research questions: which are the bonds of interaction among the subsystems in this process and who are the agents involved? The systemic approach not only diagnosed a social group, formed by MSE of Ribeirão Preto and Sertãozinho, public authorities and support entities, but could also delineate answers that aimed the clarification of obscure questions generating financial assistance to the formularization of efficient actions for the development of this system.     

Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome

Noonan syndrome is a developmental disorder characterized by short stature, facial dysmorphia, congenital heart defects and skeletal anomalies. Increased RAS-mitogen-activated protein kinase (MAPK) signaling due to PTPN11 and KRAS mutations causes 50% of cases of Noonan syndrome. Here, we report that 22 of 129 individuals with Noonan syndrome without PTPN11 or KRAS mutation have missense mutations in SOS1, which encodes a RAS-specific guanine nucleotide exchange factor. SOS1 mutations cluster at codons encoding residues implicated in the maintenance of SOS1 in its autoinhibited form. In addition, ectopic expression of two Noonan syndrome-associated mutants induces enhanced RAS and ERK activation. The phenotype associated with SOS1 defects lies within the Noonan syndrome spectrum but is distinctive, with a high prevalence of ectodermal abnormalities but generally normal development and linear growth. Our findings implicate gain-of-function mutations in a RAS guanine nucleotide exchange factor in disease for the first time and define a new mechanism by which upregulation of the RAS pathway can profoundly change human development.     

Muscle lipofuscin content and satellite cell volume is increased after high altitude exposure in humans

Muscle ultrastructural changes during a typical expedition to the Himalayas were analyzed by taking muscle biopsies from seven climbers before and after their sojourn at high altitude (over 5000 m for 8 weeks). M. vastus lateralis samples were analyzed morphometrically from electron micrographs. A quantitative evaluation was made of lipofuscin, satellite cells and myonuclei. Significant increases of the volume densities of lipofuscin (+ 235%) and satellite cells (+ 215%) were observed.