Swiss Democracy on the Web 2010 : Society and Politics in a Connected Age

The rapid adoption of online media like Facebook, Twitter or Wikileaks leaves us with little time to think. Where is information technology taking us, our society and our democratic institutions ? Is the Web replicating social divides that already exist offline or does collaborative technology pave the way for a more equal society ? How do we find the right balance between openness and privacy ? Can social media improve civic participation or do they breed superficial exchange and the promotion of false information ? These and lots of other questions arise when one starts to look at the Internet, society and politics. The first part of this paper gives an overview of the social changes that occur with the rise of the Web. The second part serves as an overview on how the Web is being used for political participation in Switzerland and abroad. Le développement rapide de nouveaux médias comme Facebook, Twitter ou Wikileaks ne laisse que peu de temps à la réflexion. Quels sont les changements que ces technologies de l'information impliquent pour nous, notre société et nos institutions démocratiques ? Internet ne fait-il que reproduire des divisions sociales qui lui préexistent ou constitue-t-il un moyen de lisser et d'égaliser ces mêmes divisions ? Comment trouver le bon équilibre entre transparence et respect de la vie privée ? Les médias sociaux permettent-ils de stimuler la participation politique ou ne sont-ils que le vecteur d'échanges superficiels et de fausses informations ? Ces questions, parmi d'autres, émergent rapidement lorsque l'on s'intéresse à la question des liens entre Internet, la société et la politique. La première partie de ce cahier est consacrée aux changements sociaux générés par l'émergence et le développement d'Internet. La seconde fait l'état des lieux de la manière dont Internet est utilisé pour stimuler la participation politique en Suisse et à l'étranger.

Monitoring of posture allocations and activities by a shoe-based wearable sensor.

Monitoring of posture allocations and activities enables accurate estimation of energy expenditure and may aid in obesity prevention and treatment. At present, accurate devices rely on multiple sensors distributed on the body and thus may be too obtrusive for everyday use. This paper presents a novel wearable sensor, which is capable of very accurate recognition of common postures and activities. The patterns of heel acceleration and plantar pressure uniquely characterize postures and typical activities while requiring minimal preprocessing and no feature extraction. The shoe sensor was tested in nine adults performing sitting and standing postures and while walking, running, stair ascent/descent and cycling. Support vector machines (SVMs) were used for classification. A fourfold validation of a six-class subject-independent group model showed 95.2% average accuracy of posture/activity classification on full sensor set and over 98% on optimized sensor set. Using a combination of acceleration/pressure also enabled a pronounced reduction of the sampling frequency (25 to 1 Hz) without significant loss of accuracy (98% versus 93%). Subjects had shoe sizes (US) M9.5-11 and W7-9 and body mass index from 18.1 to 39.4 kg/m2 and thus suggesting that the device can be used by individuals with varying anthropometric characteristics.

The endoplasmic reticulum: a sensor of cellular stress that modulates immune responses.

Many inflammatory and infectious diseases are characterized by the activation of signaling pathways steaming from the endoplasmic reticulum (ER). These pathways, primarily associated with loss of ER homeostasis, are emerging as key regulators of inflammation and infection. Recent advances shed light on the mechanisms linking ER-stress and immune responses.

Frame detection over the semantic web

In the past, research in ontology learning from text has mainly focused on entity recognition, taxonomy induction and relation extraction. In this work we approach a challenging research issue: detecting semantic frames from texts and using them to encode web ontologies. We exploit a new generation Natural Language Processing technology for frame detection, and we enrich the frames acquired so far with argument restrictions provided by a super-sense tagger and domain specializations. The results are encoded according to a Linguistic MetaModel, which allows a complete translation of lexical resources and data acquired from text, enabling custom transformations of the enriched frames into modular ontology components.

Domain shuffling in a sensor protein contributed to the evolution of insect pathogenicity in plant-beneficial Pseudomonas protegens.

Pseudomonas protegens is a biocontrol rhizobacterium with a plant-beneficial and an insect pathogenic lifestyle, but it is not understood how the organism switches between the two states. Here, we focus on understanding the function and possible evolution of a molecular sensor that enables P. protegens to detect the insect environment and produce a potent insecticidal toxin specifically during insect infection but not on roots. By using quantitative single cell microscopy and mutant analysis, we provide evidence that the sensor histidine kinase FitF is a key regulator of insecticidal toxin production. Our experimental data and bioinformatic analyses indicate that FitF shares a sensing domain with DctB, a histidine kinase regulating carbon uptake in Proteobacteria. This suggested that FitF has acquired its specificity through domain shuffling from a common ancestor. We constructed a chimeric DctB-FitF protein and showed that it is indeed functional in regulating toxin expression in P. protegens. The shuffling event and subsequent adaptive modifications of the recruited sensor domain were critical for the microorganism to express its potent insect toxin in the observed host-specific manner. Inhibition of the FitF sensor during root colonization could explain the mechanism by which P. protegens differentiates between the plant and insect host. Our study establishes FitF of P. protegens as a prime model for molecular evolution of sensor proteins and bacterial pathogenicity.

Glucose sensing by the hepatoportal sensor is GLUT2-dependent: in vivo analysis in GLUT2-null mice.

In the preceding article, we demonstrated that activation of the hepatoportal glucose sensor led to a paradoxical development of hypoglycemia that was associated with increased glucose utilization by a subset of tissues. In this study, we tested whether GLUT2 plays a role in the portal glucose-sensing system that is similar to its involvement in pancreatic beta-cells. Awake RIPGLUT1 x GLUT2-/- and control mice were infused with glucose through the portal (Po-) or the femoral (Fe-) vein for 3 h at a rate equivalent to the endogenous glucose production rate. Blood glucose and plasma insulin concentrations were continuously monitored. Glucose turnover, glycolysis, and glycogen synthesis rates were determined by the 3H-glucose infusion technique. We showed that portal glucose infusion in RIPGLUT1 x GLUT24-/- mice did not induce the hypoglycemia observed in control mice but, in contrast, led to a transient hyperglycemic state followed by a return to normoglycemia; this glycemic pattern was similar to that observed in control Fe-mice and RIPGLUT1 x GLUT2-/- Fe-mice. Plasma insulin profiles during the infusion period were similar in control and RIPGLUT1 x GLUT2-/- Po- and Fe-mice. The lack of hypoglycemia development in RIPGLUT1 x GLUT2-/- mice was not due to the absence of GLUT2 in the liver. Indeed, reexpression by transgenesis of this transporter in hepatocytes did not restore the development of hypoglycemia after initiating portal vein glucose infusion. In the absence of GLUT2, glucose turnover increased in Po-mice to the same extent as that in RIPGLUT1 x GLUT2-/- or control Fe-mice. Finally, co-infusion of somatostatin with glucose prevented development of hypoglycemia in control Po-mice, but it did not affect the glycemia or insulinemia of RIPGLUT1 x GLUT2-/- Po-mice. Together, our data demonstrate that GLUT2 is required for the function of the hepatoportal glucose sensor and that somatostatin could inhibit the glucose signal by interfering with GLUT2-expressing sensing units.

The AO comprehensive classification of pediatric long-bone fractures: a web-based multicenter agreement study.

The first AO comprehensive pediatric long-bone fracture classification system has been proposed following a structured path of development and validation with experienced pediatric surgeons. A Web-based multicenter agreement study involving 70 surgeons in 15 clinics and 5 countries was conducted to assess the reliability and accuracy of this classification when used by a wide range of surgeons with various levels of experience. Training was provided at each clinic before the session. Using the Internet, participants could log in at any time and classify 275 supracondylar, radius, and tibia fractures at their own pace. The fracture diagnosis was made following the hierarchy of the classification system using both clinical terminology and codes. kappa coefficients for the single-surgeon diagnosis of epiphyseal, metaphyseal, or diaphyseal fracture type were 0.66, 0.80, and 0.91, respectively. Median accuracy estimates for each bone and type were all greater than 80%. Depending on their experience and specialization, surgeons greatly varied in their ability to classify fractures. Pediatric training and at least 2 years of experience were associated with significant improvement in reliability and accuracy. Kappa coefficients for diagnosis of specific child patterns were 0.51, 0.63, and 0.48 for epiphyseal, metaphyseal, and diaphyseal fractures, respectively. Identified reasons for coding discrepancies were related to different understandings of terminology and definitions, as well as poor quality radiographic images. Results supported some minor adjustments in the coding of fracture type and child patterns. This classification system received wide acceptance and support among the surgeons involved. As long as appropriate training could be performed, the system classification was reliable, especially among surgeons with a minimum of 2 years of clinical experience. We encourage broad-based consultation between surgeons' international societies and the use of this classification system in the context of clinical practice as well as prospectively for clinical studies.

Hyperpolarized lithium-6 as a sensor of nanomolar contrast agents.

Lithium is widely used in psychotherapy. The (6)Li isotope has a long intrinsic longitudinal relaxation time T(1) on the order of minutes, making it an ideal candidate for hyperpolarization experiments. In the present study we demonstrated that lithium-6 can be readily hyperpolarized within 30 min, while retaining a long polarization decay time on the order of a minute. We used the intrinsically long relaxation time for the detection of 500 nM contrast agent in vitro. Hyperpolarized lithium-6 was administered to the rat and its signal retained a decay time on the order of 70 sec in vivo. Localization experiments imply that the lithium signal originated from within the brain and that it was detectable up to 5 min after administration. We conclude that the detection of submicromolar contrast agents using hyperpolarized NMR nuclei such as (6)Li may provide a novel avenue for molecular imaging.

The International LAM Registry: a component of an innovative web-based clinician, researcher, and patient-driven rare disease research platform.

BACKGROUND: A relative inability to capture a sufficiently large patient population in any one geographic location has traditionally limited research into rare diseases. METHODS AND RESULTS: Clinicians interested in the rare disease lymphangioleiomyomatosis (LAM) have worked with the LAM Treatment Alliance, the MIT Media Lab, and Clozure Associates to cooperate in the design of a state-of-the-art data coordination platform that can be used for clinical trials and other research focused on the global LAM patient population. This platform is a component of a set of web-based resources, including a patient self-report data portal, aimed at accelerating research in rare diseases in a rigorous fashion. CONCLUSIONS: Collaboration between clinicians, researchers, advocacy groups, and patients can create essential community resource infrastructure to accelerate rare disease research. The International LAM Registry is an example of such an effort. 82.

An Adeno-Associated Virus-Based Intracellular Sensor of Pathological Nuclear Factor-κB Activation for Disease-Inducible Gene Transfer.

Stimulation of resident cells by NF-κB activating cytokines is a central element of inflammatory and degenerative disorders of the central nervous system (CNS). This disease-mediated NF-κB activation could be used to drive transgene expression selectively in affected cells, using adeno-associated virus (AAV)-mediated gene transfer. We have constructed a series of AAV vectors expressing GFP under the control of different promoters including NF-κB -responsive elements. As an initial screen, the vectors were tested in vitro in HEK-293T cells treated with TNF-α. The best profile of GFP induction was obtained with a promoter containing two blocks of four NF-κB -responsive sequences from the human JCV neurotropic polyoma virus promoter, fused to a new tight minimal CMV promoter, optimally distant from each other. A therapeutical gene, glial cell line-derived neurotrophic factor (GDNF) cDNA under the control of serotype 1-encapsidated NF-κB -responsive AAV vector (AAV-NF) was protective in senescent cultures of mouse cortical neurons. AAV-NF was then evaluated in vivo in the kainic acid (KA)-induced status epilepticus rat model for temporal lobe epilepsy, a major neurological disorder with a central pathophysiological role for NF-κB activation. We demonstrate that AAV-NF, injected in the hippocampus, responded to disease induction by mediating GFP expression, preferentially in CA1 and CA3 neurons and astrocytes, specifically in regions where inflammatory markers were also induced. Altogether, these data demonstrate the feasibility to use disease-activated transcription factor-responsive elements in order to drive transgene expression specifically in affected cells in inflammatory CNS disorders using AAV-mediated gene transfer.

Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) but not PPARalpha serves as a plasma free fatty acid sensor in liver.

Peroxisome proliferator-activated receptor alpha (PPARalpha) is an important transcription factor in liver that can be activated physiologically by fasting or pharmacologically by using high-affinity synthetic agonists. Here we initially set out to elucidate the similarities in gene induction between Wy14643 and fasting. Numerous genes were commonly regulated in liver between the two treatments, including many classical PPARalpha target genes, such as Aldh3a2 and Cpt2. Remarkably, several genes induced by Wy14643 were upregulated by fasting independently of PPARalpha, including Lpin2 and St3gal5, suggesting involvement of another transcription factor. Using chromatin immunoprecipitation, Lpin2 and St3gal5 were shown to be direct targets of PPARbeta/delta during fasting, whereas Aldh3a2 and Cpt2 were exclusive targets of PPARalpha. Binding of PPARbeta/delta to the Lpin2 and St3gal5 genes followed the plasma free fatty acid (FFA) concentration, consistent with activation of PPARbeta/delta by plasma FFAs. Subsequent experiments using transgenic and knockout mice for Angptl4, a potent stimulant of adipose tissue lipolysis, confirmed the stimulatory effect of plasma FFAs on Lpin2 and St3gal5 expression levels via PPARbeta/delta. In contrast, the data did not support activation of PPARalpha by plasma FFAs. The results identify Lpin2 and St3gal5 as novel PPARbeta/delta target genes and show that upregulation of gene expression by PPARbeta/delta is sensitive to plasma FFA levels. In contrast, this is not the case for PPARalpha, revealing a novel mechanism for functional differentiation between PPARs.