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Background: Nerve injury induced protein 1 (Ninjurin 1 (Ninj1)) was first identified in Schwann cells and neurons contributing to cell adhesion and nerve regeneration. Recently, the role of Ninj1 has been linked to inflammatory processes in the central nervous system where functional repression reduced leukocyte infiltration and clinical disease activity during experimental autoimmune encephalomyelitis in mice [1]. But Ninj1 is also expressed outside the nervous system in various organs such as the liver and kidney as well as on leukocytes [2,3]. Therefore, we hypothesized that Ninj1 contributes to inflammation in general; that is, also outside the nervous system, with special interest in the pathogenesis of sepsis.
Methods: Ninj1 was repressed by transfecting HMEC-1 cells, a human dermal microvascular endothelial cell line with siRNA targeting Ninj1 (siNinj1) or a negative control (siC). Subsequently, cells were stimulated with 100 ng/ml LPS (TLR4 agonist), 3 μg/ml LTA (TLR2 agonist) or 100 n/ml poly(I:C) (TLR3 agonist) for 3 hours. The inflammatory response was analyzed by real-time PCR. In addition, transmigration of neutrophils across a HMEC-1 monolayer was measured using transwell plates (pore size 3 μm).
Results: Repression of Ninj1 by siRNA reduced Ninj1 mRNA expression in HMEC about 90% (Figure 1A). Reduced Ninj1 expression decreased neutrophil migration to 62.5% (Figure 1B) and TLR signaling. In detail, knockdown of Ninj1 significantly reduced TLR-2 and TLR-4 triggered expression of ICAM-1 and IL-6 (Figure 1C,D) while poly(I:C)-induced expression was only slightly reduced. To analyze a more specific TLR-3 target, we measured IP-10 mRNA expression, which was also significantly reduced in siNinj1-transfected cells (Figure 1E).
Conclusion: Our in vitro data strongly indicated that Ninj1 is involved in regulation of TLR signaling and therewith contributes to inflammation. In vivo experiments will clarify its impact on systemic inflammation.
The debates about the interrelations between reason and law have undergone a change after the eighteenth century. References to the recta ratio of jusnaturalistic tradition have not disappeared, but other comprehensions of legal reason have developed. The European debate over legal positivist science has contributed to this in a manifestation of the rationality of law. This transformation may be considered the basis for the development of true “legal technologies” throughout the twentieth century. On the other hand, in the context of theories of positive law which have taken the relation between ethics and legal reason as a problem, the formation of discourses on coercion (Austin and Holmes), on validity (Kelsen and Hart) and on justification (Alexy and Dworkin) has also contributed to the emergence of new models of legal rationality. In this paper, it is highlighted that the construction of these models is linked to the “points of view” which theories have proposed as legitimate for the interpretation of legal phenomenon. And it is suggested that the discussion over points of view (defined as “focuses”, term which is close to the notion of “attitude”, “stance” or “place of speech”) may aid in the debate on the normativity of law.
The role of experts grows in the present and that is, in part, justifiable: as complexity rises, the ones who deliberate feel the need of the help of those who have know-how in specific fields. The question that must be asked revolves around the type of expectations developed in modern societies regarding what experts can do. Though specialization is not a peculiarity of our time (the process can be observed since human beings became sedentary); it has presently gained specific characteristics. Two aspects of modern life are particularly significant on that matter: (i.) the fact that the economic system is based on excitation of new needs (and no longer on the demand for satisfaction of needs); (ii.) the growing pursuit for total administration of conflicts. These factors are constitutive of what Gadamer sees as a great threat to our civilization: the excessive emphasis given in our time to the human ability to adapt. A specific ability is demanded from individuals: the capability of making an apparatus functions properly. Less resistance and more adaptability is requested, and because of that, autonomous thought - that is, not determined by the function it has in a system – is devalued. The threat we currently face is that the abilities of a good technocrat become the only qualities demanded from those who are responsible for practical decisions (especially in politics and law). Teleological reason, that guides the activity of specialists (and requires know-how in a specific area and consists in choosing means to reach a previously established goal), should not substitute practical reason, as the former requires adaptability to experience (not to a plan that was previously established) and is grounded on solidarity. In order to discuss the limits of the activity of specialists, the paper looks back to phrónesis and the way ancient Greeks set boundaries - this exercise should help raising new questions revolving the matter.
H. L. A. Hart thought that a theory of law can be purely descriptive and called his theory a “descriptive sociology”. One of his great contributions to modern legal theory is his emphasis on the internal aspect of social rules. According to him, a theory of law can be built on the basis of the description of the participants’ view without sharing with it. This descriptivism is totally rejected by Dworkin, who propagates a theory that denies a sharp separation between a legal theory and its implications for adjudication. For Dworkin, a legal theory is only possible as a theory with “the internal, participants’ point of view”. Dworkin’s position implies a radicalization of legal theory that will transform the statement of an external point of view to that of an internal one. For Dworkin, the descriptivism bases on the sociological concept of law, which is an “imprecise criterial concept” and is “not sufficiently precise to yield philosophically interesting essential features.”Hart’s position is vulnerable because it takes an impure form of descriptivism that still draws a categorical distinction between fact and norm. This theoretical impurity results from the ambiguity of interpreting the internal aspect of rules. A strategy to rescue the Hart’s project is to radicalize his descriptivism with Luhmann's systems theory. Adapting the systems theoretical distinction between internal and external observation of law with all its implications for the explanation of the legal system and legal communications, Hart’s descriptivism finally attains its pure form, which is not only a distinctive paradigm of legal theory, but also possesses the potentialities to clarify its relationship to the legal theory based on the internal aspect of law.
In this article, I examine how open borders can serve the idea of global distributive justice by asking how or how not the existing practices of immigration to rich countries may contribute to global economic redistribution. There are two observations. First, migration is not the redistributive option that anyone has an equal access. In order to make use of migration as a means of global redistribution, rich countries need to provide a chance to migrate to those who cannot afford movement by themselves. Second, as long as brain-drain problems happen, what the perspective of global distributive justice requires is the compensation for some educational cost of raising professionals or some control of their movement. Immigration admissions largely focusing on getting highly skilled professionals may not serve the idea of global redistribution.
Open Online Course als Kursformat? : Konzept und Ergebnisse des Kurses "Zukunft des Lernens" 2011
(2012)
Basierend auf dem Konzept des Connectivismus entwickelte sich in den letzten fünf bis sechs Jahren ein neues offenes Kursformat: die Open Online Courses, die als so genannte MOOCs (Massive Open Online Courses) teilweise bis über 100.000 Teilnehmende anzogen. In dem Beitrag wird mit Bezug auf die konzeptionellen Ursprünge im Connectivismus das Format der Open Online Courses erläutert und Erfahrungen aus dem ersten deutschsprachigen Kurs dieser Art beschrieben, dem Kurs „Zukunft des Lernens“, den im Sommer 2011 studiumdigitale, die zentrale E-Learning-Einrichtung der Universität Frankfurt, der Weiterbildungsblogger Jochen Robes in Kooperation mit der GMW und dem Zentrum für Lehrerbildung der Universität durchführten. Der Kurs zog ca. 900 Interessierte an, die sich in verschiedenen online Medien beteiligten. Der Beitrag beschreibt den Kursverlauf, gibt einen Überblick über technische Umsetzung und Betreuungsformen und stellt neben Betrachtungen zum Transfer die Ergebnisse aus der Teilnehmerbefragung vor.
Open Online Courses als Kursformat? Konzept und Ergebnisse des Kurses "Zukunft des Lernens" 2011
(2012)
2011 starteten studiumdigitale, die zentrale eLearning-Einrichtung der Universität Frankfurt/M, und der Weiterbildungsblogger Jochen Robes den ersten deutschsprachigen Open Online Course unter dem Titel „Die Zukunft des Lernens“1. In 14 Wochen wurden in wöchentlichem Rhythmus 14 Themen behandelt, die sich rund um den Einsatz verschiedener Technologien in Bildungsprozessen und auch das Kursformat selbst drehten. Dieser Beitrag stellt die Bezüge des Open Online Courses zu seiner Herkunft und den ersten Kursen dieser Art in Kanada und USA her, bezieht sich auf die theoretischen und konzeptionellen Fundierungen dieses Ansatzes und stellt die Ergebnisse aus dem Kursverlauf und der abschließenden Befragung der Teilnehmenden vor.
Background: Undergoing systemic inflammation, the innate immune system releases excessive proinflammatory mediators, which finally can lead to organ failure. Pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs), form the interface between bacterial and viral toxins and innate immunity. During sepsis, patients with diagnosed adrenal gland insufficiency are at high risk of developing a multiorgan dysfunction syndrome, which dramatically increases the risk of mortality. To date, little is known about the mechanisms leading to adrenal dysfunction under septic conditions. Here, we investigated the sepsis-related activation of the PRRs, cell inflammation, and apoptosis within adrenal glands.
Methods: Two sepsis models were performed: the polymicrobial sepsis model (caecal ligation and puncture (CLP)) and the LTA-induced intoxication model. All experiments received institutional approval by the Regierungspräsidium Darmstadt. CLP was performed as previously described [1], wherein one-third of the caecum was ligated and punctured with a 20-gauge needle. For LTA-induced systemic inflammation, TLR2 knockout (TLR2-/-) and WT mice were injected intraperitoneally with pure LTA (pLTA; 1 mg/kg) or PBS for 2 hours. To detect potential direct adrenal dysfunction, mice were additionally injected with adrenocorticotropic hormone (ACTH; 100 μg/kg) 1 hour after pLTA or PBS. Adrenals and plasma samples were taken. Gene expressions in the adrenals (rt-PCR), cytokine release (multiplex assay), and the apoptosis rate (TUNEL assay) within the adrenals were determined.
Results: In both models, adrenals showed increased mRNA expression of TLR2 and TLR4, various NLRs, cytokines as well as inflammasome components, NADPH oxidase subunits, and nitric oxide synthases (data not shown). In WT mice, ACTH alone had no effect on inflammation, while pLTA or pLTA/ACTH administration showed increased levels of the cytokines IL-1β, IL-6, and TNFα. TLR2-/- mice indicated no response as expected (Figure 1, left). Interestingly, surviving CLP mice showed no inflammatory adrenal response, whereas nonsurvivors had elevated cytokine levels (Figure 1, right). Additionally, we identified a marked increase in apoptosis of both chromaffin and steroid-producing cells in adrenal glands obtained from mice with sepsis as compared with their controls (Figure 2).
...
Conclusion: Taken together, sepsis-induced activation of the PRRs may contribute to adrenal impairment by enhancing tissue inflammation, oxidative stress and culminate in cellular apoptosis, while mortality seems to be associated with adrenal inflammation.
Der religiöse Pluralismus innerhalb der multikulturellen Gesellschaft erfordert vom Staat das Bemühen, die wechselseitige Achtung nicht nur zwischen Personen mit unterschiedlichen religiösen Glaubensüberzeugungen, sondern auch zwischen Glaubenden und Nicht-Glaubenden sicherzustellen. In diesem Kontext wird es für die vom Staat übernommene Funktion entscheidend sein, rechtzeitig zu beurteilen, ob er eine aktive und positive Rolle als eine Institution spielt, welche dafür sorgt, dass die Religionsfreiheit der Einzelnen und der Gruppen geachtet wird. Im Vorliegenden werden einige Gefahren und Bedrohungen für die Religionsfreiheit in der heutigen Gesellschaft analysiert und eine kritische Betrachtung als Antwort auf diese Krisensituation vorgelegt. Konkret werden die folgenden Punkte erörtert: 1. Der Glaube, daß die Religion nicht mit den Werten einer modernen, liberalen Gesellschaft zu vereinbaren ist. 2. Die Konfessionalisierung des Staates. 3. Der Missbrauch der staatlichen Macht, um die Präferenzen der Bürger durch absichtliche Änderungen im sozialen Kontext zu beeinflussen. 4. Die unnötigen Behinderungen und Beschränkung des Rechts auf Verweigerung aus Gewissengründen, die von einem falschen Verständnisses desselben herrühren. 5. Die Verherrlichung eines falsch verstandenen, radikalen Individualismus. 6. Ein Verständnis des Grundsatzes der Nichtdiskriminierung als ,,Gleichgültigkeit gegenüber den Unterschieden“.
This article considers the Brazilian Legal System and the requirements of an act performed by public administration. To do so, it presents six main chapters. The first one considers Brazilian Constitution as it regards State form, legal and judicial systems. The second chapter presents the public administration stated in the Constitution. The requirements of a public administration act are presented in the third chapter. The improbity law, which determines how public administration acts should be performed, is presented on the fourth chapter. How one of the main judicial courts of Brazil has understood this law is the topic of the fifth chapter. The sixth chapter presents a proposal of how could be Phronesis used to solve misunderstandings about improbity in the Brazilian Legal System.
Es wird eine Verbindung zwischen dem von Antiphon entwickelten infinitesimalen Berechnungsverfahren, der Theorie Verteilungsgerechtigkeit von Aristoteles, des Hebelgesetzes, der eben radialen Figuren und der Verteilung hergestellt.
Die Problemstellung stellt sich wie folgt dar: dem Kennenlernen der Gründe, die Antiphon mutmaßen ließ, die Exhaustionsmethode als ein Mittel der Bildung des Quadratur des Kreises anzusehen, Beziehungen von grundsätzlicher und historischer Art zwischen der Verteilungsgerechtigkeit und den Hebelgesetz herzustellen, ein Model der Verteilungsgerechtigkeit, basierend auf der modernen Mathematik der Verteilung, von multipler Partizipierung zu konstruieren.
Die Zielsetzungen sind:
Die These zu erstellen, dass die Exhaustionsmethode aus der Gerichtspraxis stammt; dass das Hebelgesetz und die Theorie der Proportionen von Eudoxos Modelle der Verteilungsgerechtigkeit von Aristoteles sind; weiter soll gezeigt werden, dass die ebene Verteilung der materiellen Partikel auch ein Modell der Verteilungsgerechtigkeit ist.
Das Modell der Mehrteiligkeit der Verteilung, das vorgestellt wurde, enthält zwei Arten von Freiheitsgraden, einen für den Wert der zu verteilenden Güter an jeweils einen der Beteiligten und einen zweiter Freiheitsgrad für die verschieden Ebene zwischen den Beteiligten im Falle der Ungleichheit.
Keywords: Exhaustionsmethode, Hebelgesetz, Verteilungsgerechtigkeit, Verteilung.
Since de advent of what is known as new constitucionalism, jurists have faced a difficult task in order to overcome some failures of normative positivism. In this context, the judiciary has played a renewed role, which can be justified on grounds of legal theory and on institutional reasons. However, this new role has led legal philosophers to several concerns, such as the relationship between law and ethics. On one hand, Critical Legal Studies points out that the judge always acts informed by his own convictions. On the other hand, according to R. Forst (within another context, but also relevant here), this is not really a problem, because a rule can be provided with ethics, but not ethically justified. This openness of law to moral makes it difficult for the interpretative judicial discourse to be taken as claimed by K. Günther: as a discourse of application only, and not of justification. All these controversies, however, lead to a common statement: the constitutional adjudication has been exercising a different activity. Some legal systems allows such activity legitimacy in some extent, like Brazilian’s, for example, which i) states a very broad adjudication, ii) provides an extensive catalog of basic rights, and iii) contains several procedural mechanisms for their protection. This empowers the adjudication to exercise what can be called a political activity. Therefore, a series of moral issues which were once exclusive to the political arena have been brought to the judiciary, such as: gay marriage, abortion, affirmative action, religious freedom, federation, separation of powers, distribution of scarce resources. In a democracy, these moral questions ought to be mainly decided through deliberation outside the judiciary, but not always this is what happens. The paper discusses these issues, showing also how the Brazilian Supreme Court has dealt - technically, or not - with this relationship between law and justice in a complex and pluralist society.
The relation between law, moral, society and science is shifting in Brazil as it is changing in democratic contemporary societies. This paper proposes to reflect about this change in the Brazilian legal and social context. Jurisprudence and legal practice have been transformed intensively after the Brazilian redemocratization that began in 1985 and Federal Constitution of 1988. In the field of Jurisprudence (Legal Theory), a new legal theory called post-positivism progressively has been overcoming legal critical studies and legal positivism. In recent years, ideas as any moral values can be improved by law (positivism) or law is one of many oppressive institutions in capitalist society (legal critical studies – Marxism) have been losing place in legal theory. Nowadays, when Brazilian Constitution implements just society and legal system, different from the authoritarian military regime (1964 – 1985), it is difficult to work with a complete relativistic idea of law (positivism) or difficult to accept that law is necessarily oppressive in capitalistic societies. Otherwise the idea of science in law at post-positivistic point of view try to overcome in a dialectic way a pure science methodology (normativistic positivism) and the complete political and economic studies of law (critical legal studies – Marxism). After that, the text will show that Brazilian legal practice have changed intensively after post positivistic methodology of law and will reflect about same dilemmas of post-positivism in Brazil in the legal theory and practice.
In their book Principles of Biomedical Ethics, Tom Beauchamp and James Childress offer an account of bioethics, called “Principlism”, by way of specifying and balancing four clusters of principles.2 These principles are found, as the author state, in a common morality, understood as a set of universally shared moral beliefs.
This paper seeks to introduce the following questions: Does this account of Beauchamp and Childress flow from common morality in a natural way? Can their proposals claim to be endorsed by the authority of common morality? If not, in what way does Principlism contribute to bioethics?
Welche gesellschaftlichen Zwänge wirken auf die Medizin und ihre Anwender ein? Wie ist das Verhältnis von Ökonomie und medizinisch Gebotenem? Wie steht es mit der Finanzierung der nicht evidenzbasierten Behandlung? Stellen Rationierung und Rationalisierung die möglichen Prinzipien der Priorisierung dar? Führt die Priorisierung zur Qualitätsminderung oder gar Sorgfaltsverletzung? Diese Fragen behandelte der 4. Ärztetag am Dom in Frankfurt am Main. ...
A Privacy Impact Assessment (PIA) is a systematic risk assessment tool, enabling organizations to maintain compliance with data protection regulations, to manage privacy risks and to provide public benefits through the success of privacy-by-design efforts. An actual practical implementation of a PIA framework has been realized in the context of RFID applications encompassing detailed steps for the PIA process; a first successful review has been completed. The PIA also allows to introduce a pro-active mitigation of privacy risks through technical and organizational controls. The better the precautionary measures realize the relevant privacy objectives, the less likely will occur with the PIA process afterwards. The recent proposal for a far-reaching revision of the EU Data Protection Directive envisages to state a specific requirement to implement a PIA process. Indeed, since risks for privacy and non-disclosure of personal data are different in not identical circumstances, the protection measures should also be different, i.e. technology should assist in trying to achieve the (at least) second-best solution for the implementation of the data protection regime by a PIA. Insofar, privacy rules can be individualized and matched with the concrete needs in the given environment.
This paper aims to assess the arguments that claim representative democracy may be enhanced or replaced by an updated electronic version. Focusing on the dimension of elections and electioneering as the core mechanism of representative democracy I will discuss: (1) the proximity argument used to claim the necessity of filling the gap between decision-makers and stakeholders; (2) the transparency argument, which claims to remove obstacles to the publicity of power; (3) the bottom-up argument, which calls for a new form of legitimacy that goes beyond classical mediation of parties or unions; (4) the public sphere argument, referred to the problem of hierarchical relation between voters and their representatives; (5) the disintermediation argument, used to describe the (supposed) new form of democracy following the massive use of ICTs. The first way of conceptualizing e-democracy as different from mainstream 20th century representative democracy regimes is to imagine it as a new form direct democracy: this conception is often underlying contemporary studies of e-voting. To avoid some of the ingenuousness of this conception of e-democracy, we should take a step back and consider a broader range of issues than mere gerrymandering around the electoral moment. Therefore I shall problematize the abovementioned approach by analyzing a wider range of problems connected to election and electioneering in their relation with ICTs.
Pseudo-Critical Temperature and Thermal Equation of State from Nf = 2 Twisted Mass Lattice QCD
(2012)
We report about the current status of our ongoing study of the chiral limit of two-flavor QCD at finite temperature with twisted mass quarks. We estimate the pseudo-critical temperature Tc for three values of the pion mass in the range of mPS ~ 300 and 500 MeV and discuss different chiral scenarios. Furthermore, we present first preliminary results for the trace anomaly, pressure and energy density. We have studied several discretizations of Euclidean time up to Nt = 12 in order to assess the continuum limit of the trace anomaly. From its interpolation we evaluate the pressure and energy density employing the integral method. Here, we have focussed on two pion masses with mPS ~ 400 and 700 MeV.
This paper aims to discuss in which sense public hearings in supreme courts of democratic rules of law can be seen as proceduralization of popular sovereignty policies. These policies constitute expressions of a normative claim for a wider “publicization of law” by democratic states’ institutional powers and organs; a claim that becomes evident when one undertakes an intersubjective interpretation of law. This theoretical argument will be presented in the first section of the paper through a new articulation of Jürgen Habermas’ discursive theory of law and his most recent studies on the concept of political public sphere. The theoretical section gives normative and procedural criteria for the second section of the paper, which consists on a critical analysis of the procedures and practical cases of public hearings held at the Brazilian Supreme Court, constituting the first scientific study to date on the Court’s use of this legal instrument.
We explore the phase diagram of two flavour QCD at vanishing chemical potential using dynamical O(a)-improved Wilson quarks. In the approach to the chiral limit we use lattices with a temporal extent of Nt = 16 and spatial extent L = 32;48 and 64 to enable the extrapolation to the thermodynamic limit with small discretisation effects. In addition to an update on the scans at constant k, reported earlier, we present first results from scans along lines of constant physics at a pion mass of 290 MeV.We probe the transition using the Polyakov loop and the chiral condensate, as well as spectroscopic observables such as screening masses.