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In recent decades, nanopores have become a promising diagnostic tool. Protein and solid-state nanopores are increasingly used for both RNA/DNA sequencing and small molecule detection. The latter is of great importance because small molecules are difficult or expensive to detect using available methods such as HPLC or LC-MS. Moreover, DNA aptamers are an excellent detection element for sensitive and specific detection of small molecules. Here, we describe a method for the quantification of ethanolamine using Oxford Nanopore’s ready-to-use sequencing platform. To this end, we have developed a strand displacement assay using a binding ethanolamine aptamer and magnetic beads. The displaced aptamer can be detected using the MinION® nanopores and analysed/quantified using our in-house developed analysis software.

In this study, bromoalkyl glycosides were successfully synthesized in microreactor scale by Fischer glycosylation. Yields between 24 and 40% after purification were achieved using various acidic catalysts and conditions. In some experiments, yields 180% higher than with previously known methods could be achieved. This study showed also that reversed-phase flash chromatography is more successful than normal-phase flash chromatography for the purification of bromoalkyl glycosides. Furthermore, longer bromoalcohols were shown to be more compatible than shorter bromoalcohols under these reaction conditions.

This article proposes a simple and effective rotation strategy. The strategy rotates between the value-weighted market portfolio (VW) and the equal-weighted counterpart (EW) based on an implicit market signal—the lagged one-month market return. The authors report a statistically significant relation between the lagged one-month market return and the future 1/N premium, which is the return difference between the EW and VW portfolios. Building on the predictive quality and exploiting the time-varying nature of the 1/N premium, they introduce a transparent and robust investment strategy that yields superior absolute and risk-adjusted returns. TOPICS:Portfolio construction, statistical methods, security analysis and valuation, performance measurement Key Findings ▪ The authors propose a simple market-based signal to rotate between value- and equal-weighted portfolios. ▪ The signal quality is statistically significant and robust across the world. ▪ The strategy generates significant alpha after accounting for transaction costs.

In this paper we investigate the predictive power of cross-sectional volatility, skewness and kurtosis for future stock returns. Adding to the work of Maio (2015), who finds cross-sectional volatility to forecast a decline in the equity premium with high predictive power in-sample as well as out-of-sample, we highlight the additional role of cross-sectional skewness and cross-sectional kurtosis. We find cross-sectional skewness to deliver a significant contribution to the performance of cross-sectional volatility in the short run (less than 12 months forecasts), while cross-sectional skewness and cross-sectional kurtosis contribute significantly to the performance of cross-sectional volatility at horizons greater than 12 months. Furthermore, we document a clear benefit of including higher moments when disaggregating excess market returns along the value and size dimension. In this case, both cross-sectional skewness and cross-sectional kurtosis span the predictive quality towards large-cap and growth stocks. Overall, the addition of higher order cross-sectional moments significantly improves the predictive performance of cross-sectional volatility, a variable that is already regarded as having high predictive power with respect to the equity premium.

This study provides empirical evidence on the impact of board effectiveness on firm risk. The author considers the Board Shareholder Confidence Index (BSCI) to proxy for board effectiveness of firms included in the S&P TSX Composite. Risk measures considered in this study include total risk, idiosyncratic risk, systematic risk, and volatility-of-volatility. He reports statistically significant negative relationships between board effectiveness and alternative firm risk measures, except for systematic risk. This relationship is particularly strong during periods of market distress. Considering analyst coverage and strategic ownership as competing monitoring channels for board effectiveness, the author observes a substitution effect during normal market periods and a supplementary effect during periods of market distress when an investor’s level of uncertainty is high and “every little bit helps.” The findings also note the importance of corporate governance aspects in an ESG risk management framework. TOPICS:ESG investing, VAR and use of alternative risk measures of trading risk, risk management Key Findings • Board effectiveness is associated with lower levels of firm risk. • Analyst coverage acts as a substitute for board effectiveness with respect to total risk, idiosyncratic risk, and volatility-of-volatility. • Strategic ownership and ownership concentration act as a substitute for board effectiveness with respect to systematic risk. • In general, alternative monitoring mechanisms act as substitutes during normal times but are supplements during periods of distress when uncertainty is high.

This study provides finer-grained results on the financial effectiveness of ESG integration for mainstream active investment styles. We account for firm size, industry and country effects within ESG scores and introduce the concept of ESG risk materiality. Empirical evidence shows that US and European investors can raise their portfolio’s ESG level and increase risk-adjusted performance at the same time. Therefore, we add to the growing demand for sustainable products in the traditional investment industry and overcome the notion of ESG integration being a burden to traditional investment strategies.

Purpose Existing empirical evidence on the impact of environmental, social and governance (ESG) integration on momentum portfolios is limited. The combination of the two is relevant given the risk-mitigating effect of ESG criteria, as well as the existence of momentum crashes. As such, ESG might lend itself to reduce crash risk for momentum investors. Design/methodology/approach In this paper, the authors provide insight into the impact of an ESG-constrained investment universe on momentum returns. The overall investment universe is split into high and low ESG-rated segments to anylse the characteristics of momentum portfolios conditional on the ESG rating. Findings The authors document the existence of a momentum premium across European stocks and for a subset of high and lows ESG-rated stocks. However, absolute returns of momentum strategies are significantly lower if momentum strategies are pursued on a subset of high ESG stocks. Additionally, findings document a risk-mitigation effect of ESG for momentum portfolios with significantly lower returns for momentum portfolios based on low ESG stocks during periods of momentum crashes. Originality/value Research on momentum investing and the momentum premium is large and well established, yet many questions remain. A recent study by Daniel and Moskowitz (2016) has analyzed crash risk for momentum investors and identified periods of strong momentum crashes. On the other hand, the literature on ESG integration in standing investment approaches is still limited, but as demand for sustainable products is increasing, so is the demand for a better understanding of the impact of ESG integration. Consequently, the authors provide evidence on the benefits of ESG integration for momentum investors to reduce their exposure to momentum crash risk.

Exposure to ubiquitous endocrine-disrupting chemicals (EDCs) is a major public health concern. We analyzed the physiological impact of the EDC, di-2-ethylhexyl phthalate (DEHP), and found that its metabolite, mono-2-ethylhexyl phthalate (MEHP), had significant adverse effects on myeloid hematopoiesis at environmentally relevant concentrations. An analysis of the underlying mechanism revealed that MEHP promotes increases in reactive oxygen species (ROS) by reducing the activity of superoxide dismutase in all lineages, possibly via its actions at the aryl hydrocarbon receptor. This leads to a metabolic shift away from glycolysis toward the pentose phosphate pathway and ultimately results in the death of hematopoietic cells that rely on glycolysis for energy production. By contrast, cells that utilize fatty acid oxidation for energy production are not susceptible to this outcome due to their capacity to uncouple ATP production. These responses were also detected in non-hematopoietic cells exposed to alternate inducers of ROS.

Rash, photosensitivity, erythema multiforme, and the acute generalized exanthematous pustulosis (AGEP) are relatively uncommon adverse reactions of drugs. To date, the etiology is not well understood and individual susceptibility still remains unknown. Amiodarone, chlorpromazine, amitriptyline, and trimipramine are classified lysosomotropic as well as photosensitizing, however, they fail to trigger rash and pruritic papules in all individuals. Lysosomotropism is a common charcteristic of various drugs, but independent of individuals. There is evidence that the individual ability to respond to external oxidative stress is crosslinked with the elongation of long-chain fatty acids to very long-chain fatty acids by ELOVLs. ELOVL6 and ELOVL7 are sensitive to ROS induced depletion of cellular NADPH and insufficient regeneration via the pentose phosphate pathway and mitochondrial fatty acid oxidation. Deficiency of NADPH in presence of lysosomotropic drugs promotes the synthesis of C16-ceramide in lysosomes and may contribute to emerging pruritic papules of AGEP. However, independently from a lysosomomotropic drug, severe depletion of ATP and NAD(P)H, e.g., by UV radiation or a potent photosensitizer can trigger likewise the collapse of the lysosomal transmembrane proton gradient resulting in lysosomal C16-ceramide synthesis and pruritic papules. This kind of papules are equally present in polymorphous light eruption (PMLE/PLE) and acne aestivalis (Mallorca acne). The suggested model of a compartmentalized ceramide metabolism provides a more sophisticated explanation of cutaneous drug adverse effects and the individual sensitivity to UV radiation. Parameters such as pKa and ClogP of the triggering drug, cutaneous fatty acid profile, and ceramide profile enables new concepts in risk assessment and scoring of AGEP as well as prophylaxis outcome.

Conventional wisdom in Germany claims pork hocks with sauerkraut and beer. But is it really that simple? In an unbalanced cross-country panel covering 169 nations and time-series records of up to 5...

In this work, we describe a simple, fast, cheap, accurate and high-throughput method for the determination of Al, V, Cr, Mn, Fe, Co, Cu, Zn, As, Se, Mo, Cd, Sn, Ba, TI, Pb in a micro volume of urine by using inductively coupled mass spectrometry (ICP-MS) equipped with an octupole-based collision cell. The samples were directly analyzed after a simple acidification with 3% nitric acid. Validation of this method was performed by using certified urine reference material. He and H were used as collision gas for reducing polyatomic interference for most of the measured elements. Finally, we partook in an external quality assurance conducted by ISNTAND e.V. 2. Results show that our high-throughput method is ideal for detecting elements in newborns and infants because of its simplicity, speed, accuracy and low sample volume.

Assessment of hematotoxicity from environmental or xenobiotic compounds is of notable interest and is frequently assessed via the colony forming unit (CFU) assay. Identification of the mode of action of single compounds is of further interest, as this often enables transfer of results across different tissues and compounds. Metabolomics displays one promising approach for such identification, nevertheless, suitability with current protocols is restricted. Here, we combined a hematopoietic stem and progenitor cell (HSPC) expansion approach with distinct lineage differentiations, resulting in formation of erythrocytes, dendritic cells and neutrophils. We examined the unique combination of pathway activity in glycolysis, glutaminolysis, polyamine synthesis, fatty acid oxidation and synthesis, as well as glycerophospholipid and sphingolipid metabolism. We further assessed their interconnections and essentialness for each lineage formation. By this, we provide further insights into active metabolic pathways during the differentiation of HSPC into different lineages, enabling profound understanding of possible metabolic changes in each lineage caused by exogenous compounds.

Endocrine disrupting compounds (EDC) are ubiquitous in the human environment, displaying a highly relevant research topic. The impact of EDC on the differentiation of primitive cells, e.g. in hematopoiesis, is of particular interest. We found profound inhibitory effects of di-2-ethylhexyl phthalate (DEHP) on erythropoiesis and dendropoiesis, mediated via reactive oxygen species (ROS) generation. Neutrophil differentiation, however, was not affected by DEHP. ROS leads to a shift from glycolysis to the pentose phosphate pathway and diminishes ATP generation from glycolysis, ultimately resulting in apoptosis in both cell types. In neutrophils, ATP generation is held constant by active fatty acid oxidation (FAO), rendering these cells highly resistant against ROS. This relationship also holds true in HUVEC and HepG2 cells, also in combination with other organic peroxides. We, therefore, uncover a key mechanism for ROS quenching which further explains the distinct ROS quenching ability of different tissues.

Fast point-of-care (POC) diagnostics represent an unmet medical need and include applications such as lateral flow assays (LFAs) for the diagnosis of sepsis and consequences of cytokine storms and for the treatment of COVID-19 and other systemic, inflammatory events not caused by infection. Because of the complex pathophysiology of sepsis, multiple biomarkers must be analyzed to compensate for the low sensitivity and specificity of single biomarker targets. Conventional LFAs, such as gold nanoparticle dyed assays, are limited to approximately five targets—the maximum number of test lines on an assay. To increase the information obtainable from each test line, we combined green and red emitting quantum dots (QDs) as labels for C-reactive protein (CRP) and interleukin-6 (IL-6) antibodies in an optical duplex immunoassay. CdSe-QDs with sharp and tunable emission bands were used to simultaneously quantify CRP and IL-6 in a single test line, by using a single UV-light source and two suitable emission filters for readout through a widely available BioImager device. For image and data processing, a customized software tool, the MultiFlow-Shiny app was used to accelerate and simplify the readout process. The app software provides advanced tools for image processing, including assisted extraction of line intensities, advanced background correction and an easy workflow for creation and handling of experimental data in quantitative LFAs. The results generated with our MultiFlow-Shiny app were superior to those generated with the popular software ImageJ and resulted in lower detection limits. Our assay is applicable for detecting clinically relevant ranges of both target proteins and therefore may serve as a powerful tool for POC diagnosis of inflammation and infectious events.

The COVID-19 pandemic is one of the largest challenges in medicine and health care worldwide in recent decades, and it is infecting and killing increasing numbers of people every day. In this paper, we discuss the possible relationships among lysosomotropism, increasing lysosomal pH, and the SARS-CoV-2 infection and disease process, and we deduce a possible approach for treatment and prophylaxis. Lysosomotropism is a biological characteristic of small molecules, such as (hydroxyl)chloroquine, amitriptyline, NB 06, or sertraline, which is present in addition to intrinsic receptor-mediated or enzymatic pharmacological effects. Lysosomotropic compounds affect prominent inflammatory messengers, such as IL1B, CCL4, CCL20, and IL6, as well as cathepsin L dependent viral entry (fusion) into host cells. Therefore, this heterogeneous group of compounds is a promising candidate for the prevention and treatment of SARS-CoV-2 infections, as well as influenza A infections and cytokine release syndrome (CRS) triggered by bacterial or viral infections. Patients who have already taken medications with lysosomotropic compounds for other pre-existing conditions may benefit from this treatment in the COVID-19 pandemic. Increased lysosomal pH levels play an important role in the disease process in common skin disorders, such as psoriasis and atopic dermatitis, thus suggesting that affected individuals might benefit from their particular conditions in the COVID-19 pandemic. We suggest data analysis of patients with these diseases, and who are treated with lysosomotropic compounds, and, if the results are promising, subsequent clinical testing of off-label therapy with clinically approved lysosomotropic compounds in the current COVID-19 pandemic and future influenza A pandemics.

We analyze the characteristics of 22 leading equity indices and discuss common biases relative to their respective national equity markets. Findings demonstrate systematic risk-factor exposures on a universally consistent basis in form of a large-cap, low beta, growth and contrarian tilt. These systematic biases are also relevant given their knock-on effect on public changes in consumption due to a changes in net wealth, especially as more private investors are utilizing ETFs on the basis of these indices rather than delegated mandates in form of mutual or pension funds.

Considering a relatively large cross-section of ten cryptocurrencies, we test for the existence of well-known equity seasonality patterns with respect to cryptocurrency returns, volatility, trading volume and a spread estimator. Whilst we do not observe consistent and robust calendar effects in cryptocurrency returns and consequently cannot reject the weak-form market efficiency, we do observe robust patterns in trading activity. As such, trading volume, volatility and spreads are on average lower in January, on weekends and during the summer months. Besides, we also report a strong impact on the direction and significance of monthly seasonality patterns due to the stark market sell-off in January 2018, which has to be accounted for.

This article makes use of a unique dataset accounting for public trust towards alternative institutions within 27 countries, thereby yielding a local perspective on the trustworthiness of governments, the media, and the business environment as a whole. The results indicate that this local perspective adds potential value for forming rational investment decisions in a global setting that are not distorted by foreign perspectives. The author takes the perspective of a U.S. investor by considering U.S. dollar–denoted international equity indices and building trust-based portfolios, which are compared to traditional market-capitalization-weighted, GDP-weighted, ΔGDP-weighted, and equal-weighted portfolio schemes. They show that accounting for trust does entail valuable information for international equity allocation, especially with respect to fast-growing emerging economies.

Aptamer-based lateral flow assays (LFAs) are an emerging field of aptamer applications due to numerous potential applications. When compared to antibodies, potential advantages like cost effectiveness or lower batch to batch variations are evident. The development of LFAs for small molecules, however, is still challenging due to several reasons, primarily linked to target size and accessible interaction sites. In small molecule analysis, however, aptamers in many cases are preferable since immunogenicity is not required and they may exhibit even higher target selectivity. We report the first cross-recognition of a small molecule (ampicillin) and a protein (C-reactive protein), predicted by in-silico analysis, then experimentally confirmed - using two different aptamers. These features can be exploited for developing an aptamer-based LFA for label-free ampicillin detection, functioning also for analysis in milk extract. Most importantly, the principal setup denotes a novel, transferable and versatile general approach for detection of small molecules using competitive LFAs, unlikely to be generally realized by aptamer-DNA-binding otherwise.

Economists fulfilling a public mission – namely academics, Fed and government employees – demonstrate a tendency towards being pessimistic, whereas bankers in general are overly optimistic about future stock market developments. We show that these characteristics are of particular relevance and statistically significant during economic recessions and stock market downturns. Whilst investment bankers have always shown a tendency towards being optimistic, other affiliations are increasingly following their footsteps and most dominantly so for short-term forecasts. Especially during the most recent crises, their expectations of fast rebounds remained largely unsatisfied, questioning the applicability of economists’ forecasts as we move forward.

The contribution of this study is twofold. First of all, we categorise index weighting schemes along the dimension of active share and show that our division of index weighting schemes into three categories -- namely enhanced-, full replication- and sampling approaches -- corresponds to the grouping of actual mutual funds, as shown by Cremers 2009. In the second part, we analyse the role of the general market environment, by means of five cross-sectional measures, on the degree of active weight tilts observable for considered index models. We identify clear differences regarding the sensitivity towards all of the considered metrics and, thereon, confirm the necessity of a separation of weighting schemes -- commonly catalogued under the umbrella term of 'indexing' -- given their stark differences in investment patterns.

Lysosomotropism is a biological characteristic of small molecules, independently present of their intrinsic pharmacological effects. Lysosomotropic compounds, in general, affect various targets, such as lipid second messengers originating from lysosomal enzymes promoting endothelial stress response in systemic inflammation; inflammatory messengers, such as IL-6; and cathepsin L-dependent viral entry into host cells. This heterogeneous group of drugs and active metabolites comprise various promising candidates with more favorable drug profiles than initially considered (hydroxy) chloroquine in prophylaxis and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections/Coronavirus disease 2019 (COVID-19) and cytokine release syndrome (CRS) triggered by bacterial or viral infections. In this hypothesis, we discuss the possible relationships among lysosomotropism, enrichment in lysosomes of pulmonary tissue, SARS-CoV-2 infection, and transition to COVID-19. Moreover, we deduce further suitable approved drugs and active metabolites based with a more favorable drug profile on rational eligibility criteria, including readily available over-the-counter (OTC) drugs. Benefits to patients already receiving lysosomotropic drugs for other pre-existing conditions underline their vital clinical relevance in the current SARS-CoV2/COVID-19 pandemic.

Practical Applications Summary In International Equity Indexes and Public Trust, which appeared in the Summer 2018 issue of The Journal of Investing, Lars Kaiser (University of Liechtenstein) investigates the relationship between public trust and international capital flows. He examines whether public trust could serve as an alternative-weighting scheme for international equity portfolios that are traditionally weighted according to gross domestic product (GDP) or market capitalization. He finds that trust-weighted schemes perform similarly to equal-weighted schemes in terms of diversification and returns, but display lower volatility. These findings are particularly robust among emerging markets. Additionally, Kaiser finds an asymmetry between foreign and local public trust in different countries and argues that investors often make decisions based on this informational asymmetry. Overall, he suggests that public trust provides valuable additional information to investors with allocations to international equity, particularly when those allocations are in emerging markets. TOPICS:Portfolio construction, developed

Trace elements and minerals are compounds that are essential for the support of a variety of biological functions and play an important role in the formation of and the defense against oxidative stress. Here we describe a technique, allowing sequential detection of the trace elements (K, Zn, Se, Cu, Mn, Fe, Mg) in serum and whole blood by an ICP-MS method using single work-up, which is a simple, quick and robust method for the sequential measurement and quantification of the trace elements Sodium (Na), Potassium (K), Calcium (Ca), Zinc (Zn), Selenium (Se), Copper (Cu), Iron (Fe), Manganese (Mn) and Magnesium (Mg) in whole blood as well as Copper (Cu), Selenium (Se), Zinc (Zn), Iron (Fe), Magnesium (Mg), Manganese (Mn), Chromium (Cr), Nickel (Ni), Gold (Au) and Lithium (Li) in human serum. For analysis, only 100 ml of serum or whole blood is sufficient, which make this method suitable for detecting trace element deficiency or excess in newborns and infants. All samples were processed and analyzed by ICP-MS (Agilent Technologies). The accuracy, precision, linearity and the limit of quantification (LOQ), Limit of Blank (LOB) and the limit of detection (LOD) of the method were assessed. Recovery rates were between 80-130% for most of the analyzed elements; repeatabilities (Cv %) calculated were below 15% for most of the measured elements. The validity of the proposed methodology was assessed by analyzing a certified human serum and whole blood material with known concentrations for all elements; the method described is ready for routine use in biomonitoring studies.

We contribute to the ongoing debate on the existence of herding behavior in the crypto market and provide statistically significant evidence thereof. This finding is in contrast to existing empirical evidence in this field, which is primarily due to previous studies suffering from a sample bias. By introducing the concept of beta herding to the debate, we provide further robustness for our results. Moreover, we propose the concept of Bitcoin as a ‘transfer currency’ and empirically show that herding measures centered around such a transfer currency provide a more precise representation of dispersion in investors beliefs on the crypto market.

It is well understood that factor premiums, identified as contributing to portfolios risk and return, are time-varying and conditional on market phases. Besides, Amenc et al. [2016] report alternative weighting schemes not to yield similar performances, based on a common value and small-cap exposure, but identify alternative performance drivers. Thereon, we build on the existing literature regarding the factor exposure of value-weighted and equal-weighted portfolios and make us of the diversity-weighted indexing approach, in order to dynamically derive the degree of tilt towards an equal-weighting. We show that such strategies correspond to a factor rotation, whilst demonstrating favorable after-cost properties regarding risk-adjusted returns, downside deviation, portfolio concentration and tracking error. As such, it fulfills the characteristics of what Lo [2016] refers to as 'dynamic indexes.'

This study provides finer-grained results on the financial effectiveness of ESG integration for mainstream active investment styles. We account for firm-size, industry and country effects within ESG scores and introduce the concept of ESG risk materiality. Empirical evidence shows, that U.S. and European investors can raise their portfolio's ESG level and increase risk-adjusted performance at the same time. Thereby, we add to the growing demand for sustainable products in the traditional investment industry and overcome the notion of ESG integration being a burden to traditional investment strategies.

The intuitiveness and practicality of mean–variance portfolios largely depend on the accuracy of moment estimates, which are subject to large estimation errors and are conditional on time. The authors propose a model that accounts for factor dynamics in a Bayesian setting, in which they endogenously derive the effect of estimation accuracy on the posterior distribution from a linear predictive regression model. By doing so, they capture upside return potential for periods of high factor-explained variance, while constraining downside risk for periods of low predictive quality. Results are robust in a simulation and an empirical setting.

Existing studies focus on variables’ predictive quality with respect to the aggregated stock market, which per definition contains a minimum level of idiosyncratic risk and provides a favorable environment for such applications. Economic intuition suggests that the level of out-of-sample predictability decreases as we climb down the ladder from market aggregates to industries and ultimately single stock returns. Thereon, we ask the central question: Do forecasting errors from direct predictions of market components out-way the additional errors introduced by an intermediary asset pricing model? This is an early stage research note and we welcome any feedback and comments.

This study is the first to consider ``Reuters Global Asset Allocation Poll'' data, which is a monthly survey of recommended global portfolio allocations from many of the world's top investment firms, based in the U.S., UK, Continental Europe, and Japan. We find that balanced portfolio allocations by professional investors, considered in this study, closely align with the traditional 60/40 policy for asset allocation. Furthermore, we provide strong evidence on the existence of an equity home bias for investors from all four regions whereas evidence on the bond home bias tends to be equal to or stronger than for equities, however less robust across considered models. Moreover, we report a negative relation between the level of implied risk aversion and the degree of home bias and conclude that the degree of foreign asset allocation decreases in an increase of risk aversion. Finally, findings in this study indicate that about 80-90% of an investors total return can be attributed to the strategic allocation with a strong impact of economic conditions on the asset class allocation of investment professionals around the world.