Die vorliegende Abhandlung bereitet erstmals systematisch das Verhaltnis von Rechtsordnung und Wirtschaftsordnung nach der Theorie der Interdependenz der Ordnungen von Walter Eucken auf. Die meisten ...Juristen werden Walter Eucke noch mit dem Ordoliberalismus in Verbindung bringen, manche der Freiburger Schule zuordnen, die wenigsten jedoch seine 'Grundsatze der Wirtschaftspolitik' oder gar seine juristisch nicht minder gehaltvollen 'Grundlagen der Nationalokonomie' gelesen haben. Gerade die ersteren jedoch - sein nachgelassenes Hauptwerk - bilden nicht nur fur Okonomen, sondern auch fur Juristen eine uberaus anregende Lekture. Jedem Juristen, vor allem jedem Wirtschaftsrechtler, sollte eine beilaufige Beobachtung zu denken geben, die Walter Eucken in seinen 'Grundlagen der Nationalokonomie' angestellt hat: Werden der Wissenschaft in zwei Jahrtausenden nur unsere wichtigsten Rechtsnormen bekannt sein, so wird sie von unserer Wirtschaftsordnung kein wirkliches Bild gewinnen .
Whispering in Early China Petersen, Jens Østergaard
Monumenta serica,
07/03/2022, Letnik:
70, Številka:
2
Journal Article
Recenzirano
The word ouyu occurs with some frequency in early Chinese literature, signifying "to whisper" or "to murmur." It is frequently associated with expressing dissatisfaction in a furtive manner and with ...behaving in an undisciplined or indecorous way. In this article, I cover all significant instances of this word that occur in Song and pre-Song sources and find them to be about whispering for different reasons, in different contexts and with different consequences. According to the Shiji, the First Emperor of the Qin banned ouyu about the Documents and the Odes
(ouyu Shi Shu). This is the earliest attested use of the term and the passage is usually interpreted to mean that the First Emperor prohibited people from congregating to criticise his government by reference to past lore as narrated in the Documents and the Odes. This would make it the only instance in the available literature where ouyu is about anything. I argue that the commonly accepted interpretation rests on a misinterpretation of the early commentaries and suggest that the characters Shi Shu may be the result of a corruption in Shiji. What the Qin emperor outlawed was the activity of whispering as such - if people talked conspiratorially in a subdued voice, the regime saw this as proof that they harboured rebellious intentions and therefore deserved public execution, with no further evidence needed. In the last section, I discuss some literary senses of ou. I have previously argued that some of these are helpful to understanding the Qin Burning of the Books; I now dismiss them as irrelevant, since the widely attested use of ouyu as "to whisper" fully explains the Qin regime's efforts to quell criticism of its rule, as well as all later uses of the word in similar contexts.
Sickle-trait hemoglobin (HbAS) confers nearly complete protection from severe, life-threatening falciparum malaria in African children. Despite this clear protection, the molecular mechanisms by ...which HbAS confers these protective phenotypes remain incompletely understood. As a forward genetic screen for aberrant parasite transcriptional responses associated with parasite neutralization in HbAS red blood cells (RBCs), we performed comparative transcriptomic analyses of Plasmodium falciparum in normal (HbAA) and HbAS erythrocytes during both
cultivation of reference parasite strains and naturally occurring P. falciparum infections in Malian children with HbAA or HbAS. During
cultivation, parasites matured normally in HbAS RBCs, and the temporal expression was largely unperturbed of the highly ordered transcriptional program that underlies the parasite's maturation throughout the intraerythrocytic development cycle (IDC). However, differential expression analysis identified hundreds of transcripts aberrantly expressed in HbAS, largely occurring late in the IDC. Surprisingly, transcripts encoding members of the Maurer's clefts were overexpressed in HbAS despite impaired parasite protein export in these RBCs, while parasites in HbAS RBCs underexpressed transcripts associated with the endoplasmic reticulum and those encoding serine repeat antigen proteases that promote parasite egress. Analyses of P. falciparum transcriptomes from 32 children with uncomplicated malaria identified stage-specific differential expression: among infections composed of ring-stage parasites, only cyclophilin 19B was underexpressed in children with HbAS, while trophozoite-stage infections identified a range of differentially expressed transcripts, including downregulation in HbAS of several transcripts associated with severe malaria in collateral studies. Collectively, our comparative transcriptomic screen
and
indicates that P. falciparum adapts to HbAS by altering its protein chaperone and folding machinery, oxidative stress response, and protein export machinery. Because HbAS consistently protects from severe P. falciparum, modulation of these responses may offer avenues by which to neutralize P. falciparum parasites.
Sickle-trait hemoglobin (HbAS) confers nearly complete protection from severe, life-threatening malaria, yet the molecular mechanisms that underlie HbAS protection from severe malaria remain incompletely understood. Here, we used transcriptome sequencing (RNA-seq) to measure the impact of HbAS on the blood-stage transcriptome of Plasmodium falciparum in
time series experiments and
samples from natural infections. Our
time series data reveal that, during its blood stage, P. falciparum
gene expression in HbAS is impacted primarily through alterations in the abundance of gene products as opposed to variations in the timing of gene expression. Collectively, our
and
data indicate that P. falciparum adapts to HbAS by altering its protein chaperone and folding machinery, oxidative stress response, and protein export machinery. Due to the persistent association of HbAS and protection from severe disease, these processes that are modified in HbAS may offer strategies to neutralize P. falciparum.
Most severe Plasmodium falciparum infections are experienced by young children. Severe symptoms are precipitated by vascular sequestration of parasites expressing a particular subset of the ...polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion molecules. Parasites binding human endothelial protein C receptor (EPCR) through the CIDRα1 domain of certain PfEMP1 were recently associated with severe malaria in children. However, it has remained unclear to which extend the EPCR‐binding CIDRα1 domains epitomize PfEMP1 expressed in severe malaria. Here, we characterized the near full‐length transcripts dominating the var transcriptome in children with severe malaria and found that the only common feature of the encoded PfEMP1 was CIDRα1 domains. Such genes were highly and dominantly expressed in both children with severe malarial anaemia and cerebral malaria. These observations support the hypothesis that the CIDRα1‐EPCR interaction is key to the pathogenesis of severe malaria and strengthen the rationale for pursuing a vaccine or adjunctive treatment aiming at inhibiting or reducing the damaging effects of this interaction.
Synopsis
Plasmodium falciparum parasites anchor infected erythrocytes to blood vessel walls using diverse PfEMP1 adhesion proteins. Severe malaria is caused by parasites expressing a particular type of PfEMP1, which if identified could lead to development of a disease reducing adjunctive drug or vaccine intervention.
Full‐length sequences of PfEMP1 encoding transcripts were characterized in 44 children admitted to hospital with varying degrees of malaria pathology.
Genes encoding PfEMP1 predicted to bind human endothelial protein C receptor (EPCR) through their CIDRα1 domains dominated PfEMP1 transcript profiles of children suffering from cerebral malaria and/or severe malarial anaemia.
No other PfEMP1 domain or domain composition was associated with severe malaria.
These observations support the feasibility of pursuing a malaria‐reducing vaccine or drug, which interferes with the PfEMP1–EPCR interaction.
Plasmodium falciparum parasites anchor infected erythrocytes to blood vessel walls using diverse PfEMP1 adhesion proteins. Severe malaria is caused by parasites expressing a particular type of PfEMP1, which if identified could lead to development of a disease reducing adjunctive drug or vaccine intervention.
Governing climate mitigation is complex, as the recurring gap between policy intentions and actions exhibits. Interventions at the urban scale represent an opportunity to implement energy policy ...targets. Urban development projects can function as carrier to implement innovative energy solutions as ‘by-product’. To do so, planners must proactively and strategically deploy planning instruments to influence market behaviour, since project realization relies heavily on public-private interaction. This paper explores how local planning authorities use a variety of planning instruments in urban development projects that assist in implementing both planning and energy policy targets. To understand how planning instruments can be deployed deliberately to implement energy policy targets and why a specific instrument mix was chosen, this paper presents a cross-comparison of three urban development projects from Denmark, Germany and the Netherlands, which all successfully implemented innovative energy solutions. Results show that contextual differences in the processes entail the use of specific instruments to implement energy policy targets. However, the deployed instrument types, enabling factors and involved governmental levels in the technology-open processes showed a similar pattern across all three cases.
Background
Surfactant Protein D (SP‐D) is a pattern recognition molecule belonging to the family of collectins expressed in multiple human organ systems, including the lungs. Previous studies have ...shown that SP‐D levels in bronchoalveolar lavage samples decrease and serum levels increase in patients suffering from asthma, possibly due to a combination of induced SP‐D synthesis and decreased air–blood barrier integrity. The aims of this study were to investigate whether serum levels of SP‐D and common variants in the SP‐D gene were associated with asthma in adolescents and young adults.
Methods
Prospective observational study including 449 adolescents and young adults (age 11–27 years) previously diagnosed with asthma during a 2‐year period from 2003 to 2005 (0–16 years). At follow‐up from 2016 to 2017, 314 healthy controls with no history of asthma were recruited. Serum SP‐D was analyzed on samples obtained at baseline as well as samples obtained at follow‐up. SP‐D genotyping was performed for rs721917, rs2243639, and rs3088308.
Results
No differences were found in mean levels of sSP‐D and SFTPD genotype among subjects with current asthma, no current asthma, and controls. Serum SP‐D and SFTPD genotype were not associated with any clinical parameters of asthma. Furthermore, baseline sSP‐D was not associated with asthma at follow‐up.
Conclusion
Serum surfactant protein D and common SP‐D gene variants were not associated with asthma in Danish adolescents and young adults with mild to moderate asthma. Serum surfactant protein D did not demonstrate any value as a clinical biomarker of asthma.
Patients with severe COVID-19 have overwhelmed healthcare systems worldwide. We hypothesized that machine learning (ML) models could be used to predict risks at different stages of management and ...thereby provide insights into drivers and prognostic markers of disease progression and death. From a cohort of approx. 2.6 million citizens in Denmark, SARS-CoV-2 PCR tests were performed on subjects suspected for COVID-19 disease; 3944 cases had at least one positive test and were subjected to further analysis. SARS-CoV-2 positive cases from the United Kingdom Biobank was used for external validation. The ML models predicted the risk of death (Receiver Operation Characteristics-Area Under the Curve, ROC-AUC) of 0.906 at diagnosis, 0.818, at hospital admission and 0.721 at Intensive Care Unit (ICU) admission. Similar metrics were achieved for predicted risks of hospital and ICU admission and use of mechanical ventilation. Common risk factors, included age, body mass index and hypertension, although the top risk features shifted towards markers of shock and organ dysfunction in ICU patients. The external validation indicated fair predictive performance for mortality prediction, but suboptimal performance for predicting ICU admission. ML may be used to identify drivers of progression to more severe disease and for prognostication patients in patients with COVID-19. We provide access to an online risk calculator based on these findings.
Adam Smith war nicht nur einer der Begründer der Nationalökonomie, sondern auch Moralphilosoph, der in Vorlesungsmitschriften erhaltene Lectures on Jurisprudence hielt. Sein Vorhaben, eine umfassende ...Theorie des Rechts zu verfassen, konnte er nicht mehr verwirklichen und ließ von seinen Testamentsvollstreckern alle Entwürfe verbrennen. Die Hauptwerke enthalten aber so viele einschlägige Stellen, dass man sein rechtstheoretisches Konzept über weite Strecken rekonstruieren kann. Dabei ergeben sich buchstäblich brandaktuelle Einsichten: Seinen Vorschlag eines die Freiheit der Individuen einschränkenden Bankengesetzes etwa verglich er mit der Pflicht zum Bau einer gemeinsamen Brandmauer - ein angesichts des weltweiten Flächenbrandes, den die globale Finanzkrise angerichtet hat, hochmodernes Bild.
Skeletal muscle capillarization is a determining factor in gas and metabolite exchange, while its impairments may contribute to the development of sarcopenia. Studies on the potential of resistance ...training (RT) to induce angiogenesis in older muscles have been inconclusive, and effects of sequential endurance training (ET) and RT on capillarization are unknown. Healthy older men (66.5 ± 3.8 years) were engaged in either 12 weeks of habitual course observation (HC) followed by 12 weeks of RT (n = 8), or 12 weeks of high-intensity interval training (HIIT) followed by 12 weeks of RT (n = 9). At baseline, following 12 and 24 weeks, m. vastus lateralis biopsies were obtained. (Immuno-)histochemistry was used to assess indices of muscle fiber capillarization, muscle fiber morphology and succinate dehydrogenase (SDH) activity. Single periods of RT and HIIT resulted in similar improvements in capillarization and SDH activity. During RT following HIIT, improved capillarization and SDH activity, as well as muscle fiber morphology remained unchanged. The applied RT and HIIT protocols were thus similarly effective in enhancing capillarization and oxidative enzyme activity and RT effectively preserved HIIT-induced adaptations of these parameters. Hence, both, RT and HIIT, are valid training modalities for older men to improve skeletal muscle vascularization.
Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset muscle disorder, characterized by the presence of nemaline rods in muscle fibers. Phenotypic characterization in a large cohort and ...a comprehensive overview of SLONM are lacking.
We studied the clinico-pathological features, treatment and outcome in a large cohort of 76 patients with SLONM, comprising 10 new patients and 66 cases derived from a literature meta-analysis (PubMed, 1966-2016), and compared these with 15 reported HIV-associated nemaline myopathy (HIV-NM) cases. In 6 SLONM patients, we performed a targeted next-generation sequencing (NGS) panel comprising 283 myopathy genes.
SLONM patients had a mean age at onset of 52 years. The predominant phenotype consisted of weakness and atrophy of proximal upper limbs in 84%, of proximal lower limbs in 80% and both in 67%. Other common symptoms included axial weakness in 68%, as well as dyspnea in 55% and dysphagia in 47% of the patients. In 53% a monoclonal gammopathy of unknown significance (MGUS) was detected in serum. The mean percentage of muscle fibers containing rods was 28% (range 1-63%). In 2 cases ultrastructural analysis was necessary to detect the rods. The most successful treatment in SLONM patients (all with MGUS) was autologous peripheral blood stem cell therapy. A targeted NGS gene panel in 6 SLONM patients (without MGUS) did not reveal causative pathogenic variants. In a comparison of SLONM patients with and without MGUS, the former comprised significantly more males, had more rapid disease progression, and more vacuolar changes in muscle fibers. Interestingly, the muscle biopsy of 2 SLONM patients with MGUS revealed intranuclear rods, whereas this feature was not seen in any of the biopsies from patients without paraproteinemia. Compared to the overall SLONM cohort, significantly more HIV-NM patients were male, with a lower age at onset (mean 34 years). In addition, immunosuppression was more frequently applied with more favorable outcome, and muscle biopsies revealed a significantly higher degree of inflammation and necrosis in this cohort. Similar to SLONM, MGUS was present in half of the HIV-NM patients.
SLONM presents a challenging, but important differential diagnosis to other neuromuscular diseases of adult onset. Investigations for MGUS and HIV should be performed, as they require distinct but often effective therapeutic approaches. Even though SLONM and HIV-NM show some differences, there exists a large clinico-pathological overlap between the 2 entities.
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