A general approach to Bayesian portfolio optimization

We develop a general approach to portfolio optimization taking account of estimation risk and stylized facts of empirical finance. This is done within a Bayesian framework. The approximation of the posterior distribution of the unknown model parameters is based on a parallel tempering algorithm. The portfolio optimization is done using the first two moments of the predictive discrete asset return distribution. For illustration purposes we apply our method to empirical stock market data where daily asset logreturns are assumed to follow an orthogonal MGARCH process with t-distributed perturbations. Our results are compared with other portfolios suggested by popular optimization strategies. --Bayesian portfolio optimization,Gordin's condition,Markov chain Monte Carlo,Stylized facts

Fördermittel für strukturschwache Gebiete: die erfolgreiche 26-Milliarden-Euro-Subvention

Die Bund-Länder-Gemeinschaftsaufgabe "Verbesserung der regionalen Wirtschaftsstruktur" (GRW) ist ein zentraler Baustein der regionalen Wirtschaftspolitik in Deutschland. Von 1991 bis 2008 wurden auf diesem Weg gewerbliche Investitionen von Unternehmen in strukturschwachen Regionen mit 26 Milliarden Euro unterstützt. Die hier vorgestellte Wirkungsanalyse, bei der die geförderten Betriebe mit statistisch vergleichbaren, jedoch nicht geförderten "Zwillingen" verglichen werden, zeigt ein durchweg positives Bild: Geförderte Betriebe sind häufiger in forschungsintensiven Branchen tätig und die Beschäftigten sind besser qualifiziert. Geförderte Betriebe weisen zudem gegenüber nicht geförderten Betrieben einen erheblichen Wachstumsvorsprung auf, insbesondere in Ostdeutschland.Regional policy, Firm subsidies, Impact analysis, Evaluation, Statistical matching

Physiology and Pathology of Drug Hypersensitivity: Role of Human Leukocyte Antigens

Drug Hypersensitivity reactions can be distinguished in adverse drug events and adverse drug reactions. They represent a major problem in the medical scheme, since they are often underestimated. Pharmacogenetic analysis demonstrated significant associations between emerging hypersensitivity reactions and distinct genes of the HLA complex. HLA-mediated hypersensitivity reactions particularly affect skin and liver, however, impairment of the bone marrow and kidney function could also be observed. These life threatening medical conditions can be attributed to the activation of autologous drug-specific T-cells. Severe drug hypersensitivity reactions that resemble acute GvHD are linked to certain specific HLA alleles. The most common hypersensitivity reactions occur after the treatment of HLA-B*57:01+ HIV patients with abacavir and HLA-A*31:01+ or B*15:02+ epileptic patients with carbamazepine (CBZ)

Peptide Presentation Is the Key to Immunotherapeutical Success

Positive and negative selection in the thymus relies on T-cell receptor recognition of peptides presented by HLA molecules and determines the repertoire of T cells. Immune competent T-lymphocytes target cells display nonself or pathogenic peptides in complex with their cognate HLA molecule. A peptide passes several selection processes before being presented in the peptide binding groove of an HLA molecule; here the sequence of the HLA molecule’s heavy chain determines the mode of peptide recruitment. During inflammatory processes, the presentable peptide repertoire is obviously altered compared to the healthy state, while the peptide loading pathway undergoes modifications as well. The presented peptides dictate the fate of the HLA expressing cell through their (1) sequence, (2) topology, (3) origin (self/nonself). Therefore, the knowledge about peptide competition and presentation in the context of alloreactivity, infection or pathogenic invasion is of enormous significance. Since in adoptive cellular therapies transferred cells should exclusively target peptide-HLA complexes they are primed for, one of the most crucial questions remains at what stage of viral infection viral peptides are presented preferentially over self-peptides. The systematic analyzation of peptide profiles under healthy or pathogenic conditions is the key to immunological success in terms of personalized therapeutics

The influence of circumnuclear environment on the radio emission from TDE jets

Dozens of stellar tidal disruption events (TDEs) have been identified at optical, UV and X-ray wavelengths. A small fraction of these, most notably Swift J1644+57, produce radio synchrotron emission, consistent with a powerful, relativistic jet shocking the surrounding circumnuclear gas. The dearth of similar non-thermal radio emission in the majority of TDEs may imply that powerful jet formation is intrinsically rare, or that the conditions in galactic nuclei are typically unfavourable for producing a detectable signal. Here we explore the latter possibility by constraining the radial profile of the gas density encountered by a TDE jet using a one-dimensional model for the circumnuclear medium which includes mass and energy input from a stellar population. Near the jet Sedov radius of radius of 10^18 cm, we find gas densities in the range of n18 ∼ 0.1-1000 cm^−3 across a wide range of plausible star formation histories. Using one- and two-dimensional relativistic hydrodynamical simulations, we calculate the synchrotron radio light curves of TDE jets (as viewed both on and off-axis) across the allowed range of density profiles. We find that bright radio emission would be produced across the plausible range of nuclear gas densities by jets as powerful as Swift J1644+57, and we quantify the relationship between the radio luminosity and jet energy. We use existing radio detections and upper limits to constrain the energy distribution of TDE jets. Radio follow-up observations several months to several years after the TDE candidate will strongly constrain the energetics of any relativistic flow

X-ray Bright Active Galactic Nuclei in Massive Galaxy Clusters I: Number Counts and Spatial Distribution

We present an analysis of the X-ray bright point source population in 43 massive clusters of galaxies observed with the Chandra X-ray Observatory. We have constructed a catalog of 4210 rigorously selected X-ray point sources in these fields, which span a survey area of 4.2 square degrees. This catalog reveals a clear excess of sources when compared to deep blank-field surveys, which amounts to roughly 1 additional source per cluster, likely Active Galactic Nuclei (AGN) associated with the clusters. The excess sources are concentrated within the virial radii of the clusters, with the largest excess observed near the cluster centers. The average radial profile of the excess X-ray sources of the cluster are well described by a power law (N(r) ~ r^\beta) with an index of \beta ~ -0.5. An initial analysis using literature results on the mean profile of member galaxies in massive X-ray selected clusters indicates that the fraction of galaxies hosting X-ray AGN rises with increasing clustercentric radius, being approximately 5 to 10 times higher near the virial radius than in the central regions. This trend is qualitatively similar to that observed for star formation in cluster member galaxies.Comment: 18 Pages, 10 Figures, Submitted to MNRAS. Please contact Steven Ehlert ([email protected]) for higher resolution figures. Updated to reflect small changes requested by referee. This version has been accepted into MNRA

Comparison of pharmaceutical, illicit drug, alcohol, nicotine and caffeine levels in wastewater with sale, seizure and consumption data for 8 European cities

Background: Monitoring the scale of pharmaceuticals, illicit and licit drugs consumption is important to assess the needs of law enforcement and public health, and provides more information about the different trends within different countries. Community drug use patterns are usually described by national surveys, sales and seizure data. Wastewater-based epidemiology (WBE) has been shown to be a reliable approach complementing such surveys. Method: This study aims to compare and correlate the consumption estimates of pharmaceuticals, illicit drugs, alcohol, nicotine and caffeine from wastewater analysis and other sources of information. Wastewater samples were collected in 2015 from 8 different European cities over a one week period, representing a population of approximately 5 million people. Published pharmaceutical sale, illicit drug seizure and alcohol, tobacco and caffeine use data were used for the comparison. Results: High agreement was found between wastewater and other data sources for pharmaceuticals and cocaine, whereas amphetamines, alcohol and caffeine showed a moderate correlation. methamphetamine and 3,4- methylenedioxymethamphetamine (MDMA) and nicotine did not correlate with other sources of data. Most of the poor correlations were explained as part of the uncertainties related with the use estimates and were improved with other complementary sources of data. Conclusions: This work confirms the promising future of WBE as a complementary approach to obtain a more accurate picture of substance use situation within different communities. Our findings suggest further improvements to reduce the uncertainties associated with both sources of information in order to make the data more comparable.Jose Antonio Baz Lomba, Stefania Salvatore, Richard Bade, Erika Castrignanò, Ana Causanilles, Juliet Kinyua, Ann-Kathrin McCall, Pedram Ramin, Nikolaos I. Rousis, and Yeonsuk Ryu acknowledge the EU Marie-Skłodowska Curie Initial Training Network SEWPROF (Marie Curie-FP7-PEOPLE, grant number 317205) for their Early Stage Researcher grant and Emma Gracia-Lor for her Experienced Researcher grant. We thank the people and agencies who assisted in the collection of the wastewater samples, in particular Pia Ryrfors and colleagues at Vestfjorden Avløpselskap (VEAS, Oslo, Norway)

Enantiomeric profiling of chiral illicit drugs in a pan-European study

The aim of this paper is to present the first study on spatial and temporal variation in the enantiomeric profile of chiral drugs in eight European cities. Wastewater-based epidemiology (WBE) and enantioselective analysis were combined to evaluate trends in illicit drug use in the context of their consumption vs direct disposal as well as their synthetic production routes. Spatial variations in amphetamine loads were observed with higher use in Northern European cities. Enantioselective analysis showed a general enrichment of amphetamine with the R-(−)-enantiomer in wastewater indicating its abuse. High loads of racemic methamphetamine were detected in Oslo (EF = 0.49 ± 0.02). This is in contrast to other European cities where S-(+)-methamphetamine was the predominant enantiomer. This indicates different methods of methamphetamine synthesis and/or trafficking routes in Oslo, compared with the other cities tested. An enrichment of MDMA with the R-(−)-enantiomer was observed in European wastewaters indicating MDMA consumption rather than disposal of unused drug. MDA's chiral signature indicated its enrichment with the S-(+)-enantiomer, which confirms its origin from MDMA metabolism in humans. HMMA was also detected at quantifiable concentrations in wastewater and was found to be a suitable biomarker for MDMA consumption. Mephedrone was only detected in wastewater from the United Kingdom with population-normalised loads up to 47.7 mg 1000 people−1 day−1. The enrichment of mephedrone in the R-(+)-enantiomer in wastewater suggests stereoselective metabolism in humans, hence consumption, rather than direct disposal of the drug. The investigation of drug precursors, such as ephedrine, showed that their presence was reasonably ascribed to their medical use

Three years of wastewater surveillance for new psychoactive substances from 16 countries

The proliferation of new psychoactive substances (NPS) over recent years has made their surveillance complex. The analysis of raw municipal influent wastewater can allow a broader insight into community consumption patterns of NPS. This study examines data from an international wastewater surveillance program that collected and analysed influent wastewater samples from up to 47 sites in 16 countries between 2019 and 2022. Influent wastewater samples were collected over the New Year period and analysed using validated liquid chromatography - mass spectrometry methods. Over the three years, a total of 18 NPS were found in at least one site. Synthetic cathinones were the most found class followed by phenethylamines and designer benzodiazepines. Furthermore, two ketamine analogues, one plant based NPS (mitragynine) and methiopropamine were also quantified across the three years. This work demonstrates that NPS are used across different continents and countries with the use of some more evident in particular regions. For example, mitragynine has highest mass loads in sites in the United States, while eutylone and 3-methylmethcathinone increased considerably in New Zealand and in several European countries, respectively. Moreover, 2F-deschloroketamine, an analogue of ketamine, has emerged more recently and could be quantified in several sites, including one in China, where it is considered as one of the drugs of most concern. Finally, some NPS were detected in specific regions during the initial sampling campaigns and spread to additional sites by the third campaign. Hence, wastewater surveillance can provide an insight into temporal and spatial trends of NPS use

A Phenotypic Mouse Model of Basaloid Breast Tumors

Chemotherapeutic strategies that target basal-like breast tumors are difficult to design without understanding their cellular and molecular basis. Here, we induce tumors in mice by carcinogen administration, creating a phenocopy of tumors with the diagnostic and functional aspects of human triple negative disease (including EGFR expression/lack of erbB, estrogen-independent growth and co-clustering of the transcriptome with other basaloid models). These tumor strains are a complement to established mouse models that are based on mutations in Brca1 and/or p53. Tumors comprise two distinct cell subpopulations, basal and luminal epithelial cells. These cell fractions were purified by flow cytometry, and only basal cell fractions found to have tumor initiating activity (cancer stem cells). The phenotype of serially regenerated tumors was stable, and irrespective of tumor precursor cell. Tumors were passaged entirely in vivo and serial generations tested for their phenotypic stability. The relative chemo-sensitivity of basal and luminal cells were evaluated. Upon treatment with anthracycline, tumors were effectively de-bulked, but recurred; this correlated with maintenance of a high rate of basal cell division throughout the treatment period. Thus, these tumors grow as robust cell mixtures of basal bipotential tumor initiating cells alongside a luminal majority, and the cellular response to drug administration is dominated by the distinct biology of the two cell types. Given the ability to separate basal and luminal cells, and the discovery potential of this approach, we propose that this mouse model could be a convenient one for preclinical studies