Asymptotic behavior of tails and quantiles of quadratic forms of Gaussian vectors

AbstractWe derive results on the asymptotic behavior of tails and quantiles of quadratic forms of Gaussian vectors. They appear in particular in delta–gamma models in financial risk management approximating portfolio returns. Quantile estimation corresponds to the estimation of the Value-at-Risk, which is a serious problem in high dimension

The Coronavirus, Economic Policy and Economic Dynamics

The year 2020 has so far stood completely under the influence of Corona. The virus was first detected in China in late 2019, and spread all over the globe over the coming months. Nearly everyone was, and is, affected. People were afraid of getting infected and limited all sort of social interaction. Many countries implemented shutdowns with the goal of reducing the spread of the virus and saving lives. While the virus has spread, the world have experienced the severe recession in a long time. Beyond economics, Corona is present in every aspect of our daily life. On the one hand, there has been a tremendous number of touching examples of care for people at risk, and support for the parts of the population who are most affected by the consequences of the epidemic. On the other hand, some people deny the severity of the virus, question the need for social distancing and protest against public health measures. This work aims to summarise the economic literature as of June 2020 on the trade-off between saving lives and livelihoods. The authors wrote it during a Bachelor Seminar, while the whole world learned simultaneously about COVID-19

Na(+)-D-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion.

To clarify the physiological role of Na(+)-D-glucose cotransporter SGLT1 in small intestine and kidney, Sglt1(-/-) mice were generated and characterized phenotypically. After gavage of d-glucose, small intestinal glucose absorption across the brush-border membrane (BBM) via SGLT1 and GLUT2 were analyzed. Glucose-induced secretion of insulinotropic hormone (GIP) and glucagon-like peptide 1 (GLP-1) in wild-type and Sglt1(-/-) mice were compared. The impact of SGLT1 on renal glucose handling was investigated by micropuncture studies. It was observed that Sglt1(-/-) mice developed a glucose-galactose malabsorption syndrome but thrive normally when fed a glucose-galactose-free diet. In wild-type mice, passage of D-glucose across the intestinal BBM was predominantly mediated by SGLT1, independent the glucose load. High glucose concentrations increased the amounts of SGLT1 and GLUT2 in the BBM, and SGLT1 was required for upregulation of GLUT2. SGLT1 was located in luminal membranes of cells immunopositive for GIP and GLP-1, and Sglt1(-/-) mice exhibited reduced glucose-triggered GIP and GLP-1 levels. In the kidney, SGLT1 reabsorbed ∼3% of the filtered glucose under normoglycemic conditions. The data indicate that SGLT1 is 1) pivotal for intestinal mass absorption of d-glucose, 2) triggers the glucose-induced secretion of GIP and GLP-1, and 3) triggers the upregulation of GLUT2

The GTPase ARFRP1 controls the lipidation of chylomicrons in the Golgi of the intestinal epithelium

The uptake and processing of dietary lipids by the small intestine is a multistep process that involves several steps including vesicular and protein transport. The GTPase ADP-ribosylation factor-related protein 1 (ARFRP1) controls the ARF-like 1 (ARL1)-mediated Golgi recruitment of GRIP domain proteins which in turn bind several Rab-GTPases. Here, we describe the essential role of ARFRP1 and its interaction with Rab2 in the assembly and lipidation of chylomicrons in the intestinal epithelium. Mice lacking Arfrp1 specifically in the intestine (Arfrp1vil−/−) exhibit an early post-natal growth retardation with reduced plasma triacylglycerol and free fatty acid concentrations. Arfrp1vil−/− enterocytes as well as Arfrp1 mRNA depleted Caco-2 cells absorbed fatty acids normally but secreted chylomicrons with a markedly reduced triacylglycerol content. In addition, the release of apolipoprotein A-I (ApoA-I) was dramatically decreased, and ApoA-I accumulated in the Arfrp1vil−/− epithelium, where it predominantly co-localized with Rab2. The release of chylomicrons from Caco-2 was markedly reduced after the suppression of Rab2, ARL1 and Golgin-245. Thus, the GTPase ARFRP1 and its downstream proteins are required for the lipidation of chylo­microns and the assembly of ApoA-I to these particles in the Golgi of intestinal epithelial cells

Template-Directed Ligation of Tethered Mononucleotides by T4 DNA Ligase for Kinase Ribozyme Selection

Background: In vitro selection of kinase ribozymes for small molecule metabolites, such as free nucleosides, will require partition systems that discriminate active from inactive RNA species. While nucleic acid catalysis of phosphoryl transfer is well established for phosphorylation of 59 or 29 OH of oligonucleotide substrates, phosphorylation of diffusible small molecules has not been demonstrated. Methodology/Principal Findings: This study demonstrates the ability of T4 DNA ligase to capture RNA strands in which a tethered monodeoxynucleoside has acquired a 59 phosphate. The ligation reaction therefore mimics the partition step of a selection for nucleoside kinase (deoxy)ribozymes. Ligation with tethered substrates was considerably slower than with nicked, fully duplex DNA, even though the deoxynucleotides at the ligation junction were Watson-Crick base paired in the tethered substrate. Ligation increased markedly when the bridging template strand contained unpaired spacer nucleotides across from the flexible tether, according to the trends: A2.A1.A3.A4.A0.A6.A8.A10 and T2.T3.T4.T6<T1.T8.T10. Bridging T’s generally gave higher yield of ligated product than bridging A’s. ATP concentrations above 33 mM accumulated adenylated intermediate and decreased yields of the gap-sealed product, likely due to re-adenylation of dissociated enzyme. Under optimized conditions, T4 DNA ligase efficiently (.90%) joined a correctly paired, or T:G wobble-paired, substrate on the 39 side of the ligation junction while discriminating approximately 100-fold against most mispaire

Role of the small GTPase Arfrp1 on the intestinal absorption of macro nutrients

Die GTPase ARFRP1 (ARF-related protein 1) ist ein ubiquitär exprimiertes Mitglied der ARF (ADP ribosylation factor)-Familie, die als GTP-abhängige, molekulare Schalter in der Regulation des intrazellulären Transports und der Golgi-Funktion beteiligt sind. Aktives ARFRP1 assoziiert mit Membranen des trans-Golgi und kontrolliert die Rekrutierung von ARL1 und seinen Effektoren, den GRIP-domain Proteinen, an dieses Kompartiment. Die Darm-spezifische Deletion von Arfrp1 in der Maus führte zu einer frühen, postnatalen Wachstumsretardierung. Das Ziel der vorliegenden Arbeit war die Charakterisierung der Darm-spezifischen Arfrp1-Nullmutante bezüglich der Wachstumsretardierung und der Absorption von Nährstoffen. Zusätzlich sollte die Rolle von ARFRP1 für die Translokation von E-Cadherin an die Plasmamembran epithelialer Zellen untersucht werden. Arfrpvil-/--Mäuse zeigten erniedrigte Blutglucosespiegel, sowie reduzierte Konzentrationen an Triglyceriden und freien Fettsäuren im Plasma, was auf eine Malabsorption als Ursache der Wachstumsretardierung hinwies. Mehrere Experimente zeigten, dass die Absorption von Glucose und Proteinen durch die Abwesenheit von ARFRP1 nicht beeinflusst war. Im Gegensatz dazu wurde mit Hilfe eines oralen Fett- Toleranztests eine eingeschränkte Lipidaufnahme der Arfrp1vil-/--Tiere nachgewiesen, obwohl sie nach oraler Ölgabe Fettsäuren ins Darmepithels aufnahmen und dort als Lipidtropfen akkumulierten. Demnach scheint ARFRP1 an der Formation oder Sekretion von Chylomikronen beteiligt zu sein. Der Mangel von ARFRP1 in den Enterozyten der Arfrp1vil-/--Mäusen beeinflusste die Rekrutierung von Proteinen an den trans-Golgi und dessen Organisation, da ARL1 ausschließlich im Zytosol der Arfrp1vil-/--Enterozyten vorlag und der trans- Golgi-Marker TGN38 in immunhistochemischen Analysen nicht nachweisbar war. Im Gegensatz dazu war die Organisation des cis-Golgis nicht beeinträchtigt. Interessanterweise zeigten die Rab-Proteine Rab2 und Rab6, als Interaktionspartner der Effektoren von ARL1, den GRIP-domain Proteinen, eine veränderte Expression und Lokalisation in Arfrp1vil-/--Enterozyten. Dies zeigt, dass eine direkte Kaskade ARFRP1-ARL1-GRIP-Rab2/6 für die Synthese und/oder die Sekretion von Chylomikronen benötigt wird. Im zweiten Teil der Arbeit wurde die Rolle von ARFRP1 in der Regulation der Translokation von E-Cadherin an die Plasmamembran in den Epithelzellen des Darms bestätigt. In Arfrp1vil-/--Tieren verblieben große Teile von E-Cadherin in intrazellulären Membranen des Darmepithels und lagen partiell mit dem cis-Golgi-Marker GM130 ko-lokalisiert vor. Mit Hilfe von Ko-Immunopräzipitationen wurde eine direkte Interaktion von ARFRP1 mit dem E-Cadherin/β-Catenin Komplex nachgewiesen. Dies zeigt eine essentielle Rolle von ARFRP1 für die korrekte Sortierung von E-Cadherin durch den Golgi-Apparat und somit für die Lokalisation des E-Cadherin/β-Catenin Komplexes an der Zelloberfläche.The GTPase ARFRP1 (ARF-related protein 1) is a member of the family of ADP- ribosylation factors (ARFs) that operate as GTP-dependent molecular switches in the regulation of intracellular protein traffic and Golgi function. It associates with trans-Golgi membranes and controls the recruitment of ARL1 and its effectors, GRIP-domain proteins such as golgin-245. Conditional deletion of Arfrp1 in the intestinal epithelium of mice (Arfrp1vil-/-) as achieved by crossing Arfrp1flox/flox mice with transgenic mice expressing the Cre- recombinase under the villin promoter, resulted in an early postnatal growth retardation. The aim of the present work was to characterise the intestine- specific Arfrp1 nullmutant in respect to the growth retardation and to study its nutrient absorption. In addition, the specific role of ARFRP1 for the targeting of E-cadherin to the cell surface of epithelial cells should be evaluated. Arfrpvil-/- mice revealed decreased levels of blood glucose as well as triglyceride and free fatty acid concentrations in the plasma, indicating that their growth retardation is the consequence of a malabsorption. Several experiments revealed, that glucose and aminoacid absorption was not affected in Arfrpvil-/- mice. In contrast, lipid uptake elucidated by oral fat tolerance tests was impaired in Arfrp1vil-/- mice. However, Arfrp1vil-/- mice transported fatty acids into the intestinal epithelium and accumulated lipid droplets in epithelial cells after an oil bolus. This indicates that ARFRP1 is required either in chylomicron formation or their release. The lack of ARFRP1 in enterocytes of Arfrp1vil-/- mice impaired the recruitment of proteins to the trans-Golgi and altered trans-Golgi organisation, as ARL1 was exclusively located in the cytosol of Arfrp1vil-/- cells and the trans-Golgi marker TGN38 was not detectable by immunohistochemistry. In contrast, the organisation of the cis-Golgi was unaffected as detected by staining with antibodies for GM130 and p115. Interestingly, the Rab proteins Rab2 and Rab6 as interaction partners of the ARL1 effector GRIP-domain proteins, exhibited an altered expression and distribution in Arfrp1vil-/- enterocytes suggesting that a ARFRP1-ARL1-GRIP-Rab2/6 cascade is required for intestinal chylomicron production and/or release. In the second part of the present work the role of ARFRP1 in the regulation of targeting of E-cadherin to the plasma membrane was confirmed for the intestinal epithelium. Arfrp1vil-/- mice exhibited a retention of E-cadherin in intracellular membranes partially colocalising with the cis-Golgi marker GM130 in epithelial cells of the small intestine. In addition, a direct interaction of ARFRP1 with the E-cadherin/catenin complex was demonstrated by co-immunoprecipitation experiments. These data indicate that ARFRP1 is essential for the correct trafficking of E-cadherin through the Golgi and thereby required for the correct cell surface targeting of the E-cadherin complex

Asymptotic behavior of tails and quantiles of quadratic forms of Gaussian vectors

We derive results on the asymptotic behavior of tails and quantiles of quadratic forms of Gaussian vectors. They appear in particular in delta-gamma models in financial risk management approximating portfolio returns. Quantile estimation corresponds to the estimation of the Value-at-Risk, which is a serious problem in high dimension.Quadratic forms of Gaussian vectors Tail behavior Delta-gamma method Value-at-Risk Quantile estimation

Flexible RF front-end for communication in TV white spaces

A digitally tunable RF front-end for TV white space communication is presented. The front-end covers an RF frequency range of 470 MHz to 860 MHz with a signal bandwidth of 40 MHz. It is based on a heterodyne architecture with a single frequency conversion using an IF of 280 MHz. Among the frequency tunability, the transmitter provides a maximum output power of 17 dBm and the receiver an input sensitivity of -90 dBm as well as a total noise figure of 3.5 dB at maximum gain. The performance of the RF front-end is evaluated by measurements using harmonic and modulated signals