Tokenization of Assets: Security Tokens in Liechtenstein and Switzerland

Technological innovations invariably lead to legal questions being raised; the sphere of digitalization of physical documents and securities by use of blockchain and other distributed ledger technologies does not constitute an exception. While solutions for many questions can be found within the existing legal framework, some developments call for legislative measures. This paper examines the hurdles in connection with the issuance and transfer of securities by virtue of a mere digital transaction and the approaches of the Liechtenstein and Swiss legislator to overcome them. Both have recognized that entries in distributed ledgers may fulfill the same main functions as the possession of a physical document. While the focus of the selective legal adaptations in Switzerland is on the use of DLT and securities law, the Liechtenstein legislator strives towards a holistic legal and regulatory framework for the entire token economy by introduction of a new set of rules.    Le innovazioni tecnologiche portano inevitabilmente a sollevare questioni legali; l’ambito della digitalizzazione dei documenti fisici e dei titoli attraverso l'uso di blockchain e di altre tecnologie a registro distribuito non costituisce un'eccezione. Mentre le soluzioni per molte questioni possono essere trovate all'interno del quadro giuridico esistente, alcuni cambiamenti richiedono misure legislative. Questo paper esamina gli ostacoli esistenti in relazione all'emissione e al trasferimento di titoli in forza di una semplice transazione digitale e gli approcci del legislatore del Liechtenstein e di quello svizzero per superarli. Entrambi hanno riconosciuto che le caratteristiche dei registri distribuiti possono adempiere alle stesse principali funzioni del possesso di un documento fisico. Mentre in Svizzera si tratta di un adattamento normativo selettivo riferito all'uso della DLT e al diritto dei titoli, il legislatore del Liechtenstein cerca di creare un quadro giuridico e normativo olistico per l'intera economia token attraverso l'introduzione di un nuovo set di regole

Nuclear Factor-κB-Independent Anti-Inflammatory Action of Salicylate in Human Endothelial Cells

In contrast to aspirin, salicylate, its active metabolite, possesses profound anti-inflammatory properties without blocking cyclooxygenase. Inhibition of the transcription factor nuclear factor-κB (NF-κB) has been discussed to play a role in the anti-inflammatory profile of salicylate. However, NF-κB-independent effects of salicylate have been assumed but have up to now been poorly investigated. Therefore, the aim of the present study was to investigate NF-κB-independent anti-inflammatory mechanisms of salicylate in human umbilical vein endothelial cells using interleukin-4 (IL-4) as NF-κB-independent proinflammatory stimulus and P-selectin as inflammatory read-out parameter. Using quantitative real-time reverse transcriptionpolymerase chain reaction, we found that salicylate decreases IL-4-induced P-selectin expression. As judged by Western blot analysis, salicylate increased endothelial heme oxygenase-1 (HO-1) protein levels. Using both the HO-1 inhibitor tin(II) protoporphyrin IX and HO-1 antisense oligonucleotides, we causally linked the induction of HO-1 to the decrease of P-selectin. Moreover, we were interested in the signaling mechanisms leading to the up-regulation of HO-1 by salicylate. c-Jun NH2-terminal kinase (JNK) was found to be activated by salicylate, and we could causally link this activation to the induction of HO-1 by using the JNK inhibitor 1,9-pyrazoloanthrone. By applying activator protein-1 (AP-1) decoys, it was shown that the transcription factor AP-1 is crucially involved in the up-regulation of HO-1 downstream of JNK. In summary, our study introduces HO-1 as novel NF-κB-independent anti-inflammatory target of salicylate in human endothelial cells. Moreover, we elucidated the JNK/AP-1 pathway as crucial for the induction of HO-1 by salicylate

BIOMECHANICAL FACTORS FOR THE ETIOLOGY OF NAVICULAR DISEASE IN SPORTS HORSES

INTRODUCTION: Navicular disease is a common syndrome in sports horses such as gallopers, jumpers and western horses (especially quarter horses; Stashak, 1987). This syndrome causes forelimb lameness due to pain of the navicular bone (distal sesamoid of the horse digit), navicular bursitis and deep flexor tendon (DFT) affection. When horses develop navicular disease, they can no longer be used for competitive purposes, although they may still be useful for breeding purposes. Yet navicular disease is hereditary, although the mechanisms are still unclear. Nevertheless, distinct morphological variations exist in the navicular bone which are also hereditary (Ueltschi et al., 1995). Our hypothesis on the transmission of navicular disease is that morphological variability causes differences in joint load and bone stress. The aim of this study was to analyze the biomechanical effects of morphological variations of the navicular bone. METHODS: We examined 87 horses radiographically. X-rays were taken of the lateral aspects of the front toes. In the radiographs, the rotation center (center of curvature) of the coffin joint (phalanx II-phalanx III and navicular bone-phalanx II) was determined. Based on this, we constructed the lever arms of the acting forces, taking into account the diameter of the DFT. The lever arms of the proximal DFT-force and of the force of the joint between phalanx III and the navicular bone were calculated relative to the lever arm of the distal DFT-force. Taking into consideration the joint angles, we calculated the tendon and joint forces, and joint surface stresses (quasi-static inverse-dynamic calculation). RESULTS: The decisive factor for the differences in navicular mechanics is the proximal DFT lever arm. The smaller it is - relative to the distal lever arm - the more pressure will be concentrated at the distal end of the navicular bone. The larger it is, the more the pressure maxima will be shifted to the middle, and the more favorable the pressure distribution will be. Unfavorable navicular mechanics will thus occur when the bone is over-stressed in its distal border region where the distal arteries enter the bone. CONCLUSIONS: The varying morphology of the navicular bone is therefore a further explanation for the multi-factorial genesis of navicular disease. This knowledge appears all the more important because selective breeding can prevent the hereditary transmission of unfavorable navicular morphology. The radiological examination of the navicular bone is therefore, besides the classic exterior examination, a sensible screening measure for breeding (Ueltschi et al. 1995). Further, radiological examination is a sensible complement to purchase or aptitude tests. REFERENCES: Stashak, T. S. (1987). Adams’ Lameness in Horses. Philadelphia: Lea & Febiger. Ueltschi, G., Hornig, I., Stornetta, D. (1995). Beobachtungen zur Genetik der Podotrochlose. In P. F. Knezevic (Ed.), Orthopädie bei Huf- und Klauentieren. Stuttgart: Schattauer

Atrial Natriuretic Peptide, a Regulator of Nuclear Factor-κB Activation in Vivo

Natriuretic peptides (NPs) comprise a family of vasoactive hormones that play important roles in the regulation of cardiovascular and renal homeostasis. Along this line, atrial NP (ANP) (international non-proprietary name: carperitide, HANP) is an approved drug for the treatment of acute heart failure. In recent years, evidence has been given that the NP system possesses a far broader biological spectrum than the regulation of blood pressure and volume homeostasis. In fact, a substantial amount of in vitro work indicates that ANP affects important inflammatory processes and signaling pathways. Quite surprisingly, however, no information exists on the in vivo antiinflammatory potential and signaling of ANP. We show here that pretreatment of lipopolysaccharide (Salmonella abortus equi, 2.5 mg/kg)-challenged mice with ANP (5μg/kg iv, 15 min) rapidly inhibits nuclear factor-κB activation via inhibition of phosphorylation and degradation of the IκB-α protein. ANP also reduces Akt activation upon lipopolysaccharide injection. In ANP-pretreated mice, the increase of TNF-α serum concentration is markedly prevented; most importantly, the survival of these animals improved. These findings demonstrate both in vitro and in vivo an antiinflammatory profile of ANP that deserves to be further investigated in a therapeutic perspective

MAPK phosphatase-1 represents a novel antiinflammatory target of glucocorticoids in the human endothelium

Glucocorticoids are well-established anti- inflammatory drugs thought to mainly act by inhibition of proinflammatory transcription factors like NF-κB. In recent years, however, transcription factorindependent mechanisms of glucocorticoid action have been proposed, namely the influence on MAPK pathways. Here we identify MAPK phosphatase-1 (MKP-1) as a pivotal mediator of the anti-inflammatory action of glucocorticoids in the human endothelium. We applied dexamethasone (Dex) to TNF-α-activated human endothelial cells and used the adhesion molecule E-selectin as inflammatory read-out parameter. Dex is known to reduce the expression of E-selectin, which is largely regulated by NF-κB. Here, we communicate that Dex at low concentrations (1–100 nM) markedly attenuates E-selectin expression without affecting NF-κB. Importantly, Dex is able to increase the expression of MKP-1, which causes an inactivation of TNF-α-induced p38 MAPK and mediates inhibition of E-selectin expression. In endothelial MKP-1ˉ/ˉ cells differentiated from MKP-1ˉ/ˉ embryonic stem cells and in MKP-1-silenced human endothelial cells, Dex did not inhibit TNF-α-evoked E-selectin expression. Thus, our findings introduce MKP-1 as a novel and crucial mediator of the anti-inflammatory action of glucocorticoids at low concentrations in the human endothelium and highlight MKP-1 as an important and promising antiinflammatory drug target

Atrial Natriuretic Peptide Induces Mitogen-Activated Protein Kinase Phosphatase-1 in Human Endothelial Cells via Rac1 and NAD(P)H Oxidase/Nox2-Activation

The cardiovascular hormone atrial natriuretic peptide (ANP) exerts anti-inflammatory effects on tumor necrosis factor-α–activated endothelial cells by inducing mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1). The underlying mechanisms are as yet unknown. We aimed to elucidate the signaling pathways leading to an induction of MKP-1 by ANP in primary human endothelial cells. By using antioxidants, generation of reactive oxygen species (ROS) was shown to be crucially involved in MKP-1 upregulation. ANP was found to increase ROS formation in cultured cells as well as in the endothelium of intact rat lung vessels. We applied NAD(P)H oxidase (Nox) inhibitors (apocynin and gp91ds-tat) and revealed this enzyme complex to be crucial for superoxide generation and MKP-1 expression. Moreover, by performing Nox2/4 antisense experiments, we identified Nox2 as the critically involved Nox homologue. Pull-down assays and confocal microscopy showed that ANP activates the small Rho-GTPase Rac1. Transfection of a dominant-negative (RacN17) and constitutively active Rac1 mutant (RacV12) indicated that ANP-induced superoxide generation and MKP-1 expression are mediated via Rac1 activation. ANP-evoked production of superoxide was found to activate c-Jun N-terminal kinase (JNK). Using specific inhibitors, we linked ANP-induced JNK activation to MKP-1 expression and excluded an involvement of protein kinase C, extracellular signal-regulated kinase, and p38 MAPK. MKP-1 induction was shown to depend on activation of the transcription factor activator protein-1 (AP-1) by using electrophoretic mobility shift assay and AP-1 decoys. In summary, our work provides insights into the mechanisms by which ANP induces MKP-1 and shows that ANP is a novel endogenous activator of endothelial Rac1 and Nox/Nox2

Metalloporphyrins inactivate caspase-3 and -8

Activation of caspases represents one of the earliest biochemical indicators for apoptotic cell death. Therefore, measurement of caspase activity is a widely used and generally accepted method to determine apoptosis in a wide range of in vivo and in vitro settings. Numerous publications characterize the role of the heme-catabolizing enzyme heme oxygenase-1 (HO-1) in regulating apoptotic processes. Different metalloporphyrins representing inducers and inhibitors of this enzyme are often used, followed by assessment of apoptotic cell death. In the present work, we found that caspase-3-like activity, as well as activity of caspase-8 measured in either Fas (CD95) ligand-treated Jurkat T-lymphocytes or by the use of recombinant caspase-3 or -8, was inhibited by different metalloporphyrins (cobalt(III) protoporphyrin IX, tin and zinc II) protoporphyrin-IX). Moreover, employing the mouse model of Fas-induced liver apoptosis these properties of porphyrins could also be demonstrated in vivo. The metalloporphyrins were shown to inhibit caspase-3-mediated PARP cleavage. Molecular modeling studies demonstrated that porphyrins can occupy the active site of caspase-3 in an energetically favorable manner and in a binding mode similar to that of known inhibitors. The data shown here introduce metalloporphyrins as direct inhibitors of caspase activity. This finding points to the need for careful employment of metalloporphyrins as modulators of HO-1

Untersuchungen zu den Pathomechanismen der Destruktion von Faserknorpelgewebe am Beispiel des Meniskus.

Das Ziel der vorliegenden Arbeit war, ein in vitro-Modellsystem zur Destruktion des Meniskus am Beispiel des proinflammatorischen Zytokins IL-1 (Interleukin-1) zu etablieren. Die Untersuchungen wurden am Meniskusgewebe und an isolierten Meniskuszellen durchgeführt. Am Meniskusgewebe wurde der Einfluss von IL-1 auf den Abbau der Proteoglykane, die biomechanischen Eigenschaften, die Biosyntheseaktivität, die NO-Produktion und die Expression von matrix-abbauenden Proteasen untersucht. Bei den Meniskuszellen wurde der Einfluss von IL-1 auf den Transkriptionsfaktor NF-kB sowie die Expression von matrix-abbauenden Proteasen untersucht. Im Meniskusgewebe erhöhte IL-1 die GAG-Freisetzung und NO-Produktion, senkte die biomechanischen Eigenschaften sowie die Biosyntheseaktivität und induzierte eine erhöhte Expression von matrix-abbauenden Proteasen (MMP-2, MMP-3). Bei den Meniskuszellen aktivierte IL-1 den Transkriptionsfaktor NF-kB und erhöhte die Expression der Matrixmetalloproteinasen MMP-3, -9 und -13

Peer Evaluation of Team Member Effectiveness as a Formative Educational Intervention

Peer evaluation of team member effectiveness is often used to complement cooperative learning in the classroom, by holding students accountable for their team contributions. Drawing on the tenants of self-determination theory, this study investigated the impacts of formative peer evaluation in university level team-based design projects. The hypothesis was that the introduction of formative peer evaluation cycles would result in a more student-centered learning climate, increased competence, reduced doubt, and improved student learning. Two semesters were compared in this quasi-experimental study where results of peer evaluation became modifiers to students’ grades in the final project. In only one of the semesters, peer evaluation was also used multiple times formatively to provide students with feedback and encourage changes in behavior without impacting grades. When formative peer evaluation was implemented, students earned higher grades on the final project and in the course and perceived a more student-centered learning environment, more competence, and less doubt about the course

Relationship of sleep quality and health-related quality of life in adolescents according to self- and proxy ratings: a questionnaire survey

Roeser K, Eichholz R, Schwerdtle B, Schlarb A, Kübler A. Relationship of sleep quality and health-related quality of life in adolescents according to self- and proxy ratings: a questionnaire survey. Front Psychiatry. 2012;3:76:76.Introduction: Sleep disturbances are common in adolescents and adversely affect performance, social contact, and susceptibility to stress. We investigated the hypothesis of a relationship between sleep and health-related quality of life (HRQoL), and applied self- and proxy ratings. Materials and Methods: The sample comprised 92 adolescents aged 11–17 years. All participants and their parents completed a HRQoL measure and the Sleep Disturbance Scale for Children (SDSC). Children with SDSC T-scores above the normal range (above 60) were classified as poor sleepers. Results: According to self- and proxy ratings, good sleepers reported significantly higher HRQoL than poor sleepers. Sleep disturbances were significantly higher and HRQoL significantly lower in self- as compared to parental ratings. Parent-child agreement was higher for subscales measuring observable aspects. Girls experienced significantly stronger sleep disturbances and lower self-rated HRQoL than boys. Discussion: Our findings support the positive relationship of sleep and HRQoL. Furthermore, parents significantly underestimate sleep disturbances and overestimate HRQoL in their children