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An important quality attribute of a recombinant Adeno-Associated Virus (rAAV) as a therapeutic vector is its infectivity. Current assays to quantify infectious rAAV rely on coinfection with a helper virus such as adenovirus, which requires helper virus preparation and introduces additional variability. Here we describe a stable assay cell line that was generated by integrating the coding sequences for AAV Rep68 and adenovirus E4orf6 and DNA Binding Protein (DBP) under the control of inducible promoters. The Rep68 protein expression was further modulated by a ligand-responsive destabilization domain. In several benchmarks, the cell line gave comparable titers to those obtained using a classical adenovirus coinfection method. The cell line was also used to titer vectors of multiple AAV serotypes. This cell line has the potential to serve as an effective and robust tool for product quality evaluation.

Objective Kalman filtering has previously been applied to track neural model states and parameters, particularly at the scale relevant to electroencephalography (EEG). However, this approach lacks a reliable method to determine the initial filter conditions and assumes that the distribution of states remains Gaussian. This study presents an alternative, data-driven method to track the states and parameters of neural mass models (NMMs) from EEG recordings using deep learning techniques, specifically a Long Short-Term Memory (LSTM) neural network. Approach An LSTM filter was trained on simulated EEG data generated by a neural mass model using a wide range of parameters. With an appopriately customised loss function, the LSTM filter can learn the behaviour of NMMs. As a result, it can output the state vector and parameters of NMMs given observation data as the input. Main Results Test results using simulated data yielded correlations with R squared of around 0.99 and verified that the method is robust to noise and can be more accurate than a nonlinear Kalman filter when the initial conditions of the Kalman filter are not accurate. As an example of real-world application, the LSTM filter was also applied to real EEG data that included epileptic seizures, and revealed changes in connectivity strength parameters at the beginnings of seizures. Significance Tracking the state vector and parameters of mathematical brain models is of great importance in the area of brain modelling, monitoring, imaging and control. This approach has no need to specify the initial state vector and parameters, which is very difficult to do in practice because many of the variables being estimated cannot be measured directly in physiological experiments. This method may be applied using any neural mass model and, therefore, provides a general, novel, efficient approach to estimate brain model variables that are often difficult to measure.

Co-infection with Hepatitis C virus (HCV) among HIV-positive patients leads to accelerated progression of liver disease and AIDS. Due to increased HCV prevalence and incidence, co-infection requires monitoring trends among HIV-positive individuals. This will help target prevention strategies and support to reach the global goals of eliminating viral hepatitis as a public health threat. In this analysis HCV prevalence and incidence were determined for the years 1996-2019 from yearly blood samples and questionnaire details among HIV-1-positive patients, with a majority of men who have sex with men, belonging to a nationwide, multicentre observational, prospective cohort study. The results show that HCV prevalence for acute/chronic and resolved infection increased until 2014 to 12%. Since then, prevalence of acute/chronic HCV infection rapidly decreased and prevalence of resolved infections showed a steady increase. HCV incidence was highest in 2010 and lowest in 2017; however, no significant change in HCV incidence could be seen over the years. Therefore, the introduction of directly-acting antiviral agents for HCV treatment notably decreased prevalence and potentially incidence of acute/chronic HCV infection. Nevertheless, prevalence and incidence of HCV among these HIV-1-positive study participants remain high compared with the general population and justify the need for continuous HCV prevention and treatment efforts among HIV-positive individuals.

Supranational law seems to increasingly influence national law. This is also assumed to be the case for collective bargaining law, which is exposed to a superstructure of international law in addition to the determinants of European Union law. Daniel Schmidt examines the interaction of the legal systems, starting with a legal methodological approach based on the principle of sovereignty under international law and German constitutional law. On this basis, he determines the scope of the supranational provisions on collective bargaining law and answers the questions of the binding effect of the parties to collective agreements on supranational law and the interpretation of collective agreements in conformity with international and Union law.

We study the extent of cross-asset learning in financial markets by examining the spillover effects around mutual fund fire sales, which lead to a well-documented impact-reversal pattern in returns. We find that the returns of fire sale stocks spill over onto the stock returns of economic peers with a magnitude of around one-third of the original effect. These spillovers extend to liquidity and are not explained by common funding shocks or the hedging activity of liquidity providers. We conclude that they represent information spillovers due to learning from prices, thus identifying cross-asset learning as an important driver for the commonality in returns and liquidity. (JEL G11, G12, G14, G23) Received July 1, 2021; editorial decision August 30, 2021. Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.

The study of human cognition and the study of artificial intelligence (AI) have a symbiotic relationship, with advancements in one field often informing or creating new work in the other. Human cognition has many capabilities modern AI systems cannot compete with. One such capability is the detection, identification, and resolution of knowledge gaps (KGs). Using these capabilities as inspiration, we examine how to incorporate detection, identification, and resolution of KGs in artificial agents. We present a paradigm that enables research on the understanding of KGs for visual-linguistic communication. We leverage and enhance and existing KG taxonomy to identify possible KGs that can occur for visual question answer (VQA) tasks and use these findings to develop a classifier to identify questions that could be engineered to contain specific KG types for other VQA datasets. Additionally, we examine the performance of different VQA models through the lens of KGs.

Augmentals, as a type of verbal rule, have been used in political speeches either for establishing beneficial cultural values for the populace (Leigland, 2005) or for publicizing political points of view to exert control on public opinion through propaganda (Rakos, 1993). The current study conducted a functional content analysis on two presidential speeches about climate change and global warming regarding whether the United States should enter or exit the Paris Climate Agreement. The purposes of the study were to (a) examine the effects of two types of augmentals (reinforcer-establishing augmentals and punisher-establishing augmentals) on behavior change in the populace, (b) explore the effects of the types of relational frames that formed augmentals, and (c) provide guidance to the public on discriminating propaganda in media sources. The results showed different patterns in the use of augmentals in Donald Trump’s speech, which attempted to persuade the populace to support exiting the agreement, compared to Barack Obama’s speech, which attempted to persuade the populace to support entering the agreement. Several implications of the study are discussed.

We report gamma ray spectroscopy measurements of trinitite samples and analogous samples obtained from detonation sites in Nevada and Semipalatinsk, as well as in situ measurements of topsoil at the Trinity site. We also report the first isotopic composition measurements of trinitite using the novel forensics technique of decay energy spectroscopy (DES) as a complement to traditional forensics techniques. Our gamma spectroscopy and DES measurements are compared to other published results.

Aim [99mTc]Tc-PSMA-based radioguided surgery (TPRS) represents a curative approach for localized relapse of prostate cancer. For its simplified regulatory permission, the radiation protection authorities require a 99mTc- activity below the exemption limit of 10 MBq at the time of surgery. Our aim was to determine the optimal amount of radioactivity (OAR) to comply with that limit and to estimate the maximum number of TPRS procedures per year and surgeon without triggering the full monitoring obligations. Methods In this retrospective study, a dose rate meter was calibrated using measurements on phantoms and from recently injected (1 min p. i.) patients to determine the activity in the patient from measured dose rates. The effective half-life of 99mTc-PSMA-I&S in patients was determined from repeated dose rate measurements to estimate dose parameters of relevance for radiation protection. External exposures of the surgeons were measured with personal dosimeters calibrated in Hp(10). The surgeon’s finger dose Hp(0.07) is estimated from radioactivity measured in resected lymph nodes. Potenzial incorporations were estimated for an activity of 10 MBq. Results From the first 6 subsequent patients, an effective half-life of 4.15 h was observed. Assuming an operation time 24 h p. i., the OAR was 550 MBq. Operations lasting in average 2 h in a distance of 0.25 m to the patient imply a body dose for surgeons of 4.16 µSv per procedure. Based on these estimates, the surgeon’s Hp(10) is less than 1 mSv per year with up to 241 operations per year. Hp(0.07) and potential incorporation of activity do not lead to further limitations. Summary All radiation protection regulations are met with adherence to OAR recommended here without triggering the full monitoring obligations from radiation protection regulations.

Soybean oil (SBO) is a renewable material used as an alternative to conventional petroleum-derived oils in the processing of rubber composites. Upon chemical modifications, such as epoxidation, its performance in the processing of rubber can be significantly improved, as indicated by a considerable reduction of the mixing energy. Although it has been hypothesized that hydrogen bonding between functional groups (e.g., epoxy) of SBOs and silanols present on the silica surface plays a key role, there is still a lack of direct evidence supporting this hypothesis. In this work, it is demonstrated that there is an overall correlation between the epoxy concentration of SBOs and the mixing energy, consistent with the long-held hypothesis. In particular, a correlation between the SBO-silica adsorption affinity and the degree of epoxidation is revealed by a set of surface-selective solid-state nuclear magnetic resonance (ssNMR) experiments. In addition, the surface-selective ssNMR technique demonstrated in this work could also be used to evaluate the adsorption affinity of other oils and/or additives more broadly.

The Hyperspectral X-ray Imaging (HXI) project will enable non-destructive chemical-state determination of nano-scale samples in the electron microscope for nuclear safeguards applications. To efficiently measure chemical state through electron-excited X-ray emission requires a combination of wide spectral bandwidth, high resolution, and high count rate capability. We are building a next-generation X-ray detector based on an array of transition edge sensors (TESs) to make these measurements possible and routine in the scanning electron microscope (SEM). Leveraging the large pixel densities afforded by microwave multiplexing readout and continuous, uninterrupted operation of a cryogen-free dilution refrigerator, this instrument will have efficiency to allow chemical species identification of nano-scale samples in hours instead of days to weeks. We describe prototype pixel designs for this HXI instrument, comprising three pixel types that will make up the hybrid TES array. Engineering design of the integrated HXI cryostat and SEM system is in progress, with full detector commissioning expected in Spring 2021 followed closely by full-scale integration with the SEM. We also report on the commissioning of a complementary TES-based X-ray emission spectroscopy platform for bulk samples to build a spectral library for HXI sample identification.

A superconducting transition-edge sensor (TES) microcalorimeter is an ideal X-ray detector for experiments at accelerator facilities because of good energy resolution and high efficiency. To study the performance of the TES detector with a high-intensity pulsed charged-particle beam, we measured X-ray spectra with a pulsed muon beam at the Japan Proton Accelerator Research Complex (J-PARC) in Japan. We found substantial temporal shifts of the X-ray energy correlated with the arrival time of the pulsed muon beam, which was reasonably explained by pulse pileup due to the incidence of energetic particles from the initial pulsed beam.

Overexpression of the neurotensin receptor type 1 (NTS

IntroductionObjectives of this study, as part of a nation-wide HIV pre-exposure prophylaxis (PrEP) evaluation project, were to determine the incidence of infections with HIV, chlamydia, gonorrhea, syphilis, hepatitis A/B/C in persons using PrEP, and to describe the health care funded PrEP use in Germany. Additionally, factors associated with chlamydia/gonorrhea and syphilis infections were assessed.MethodsAnonymous data of PrEP users were collected at 47 HIV-specialty centers from 09/2019-12/2020. Incidence rates were calculated per 100 person years (py). Using longitudinal mixed models, we analyzed risk factors associated with sexually transmitted infections (STIs).Results4620 PrEP users were included: 99.2% male, median age 38 years (IQR 32-45), 98.6% men who have sex with men (MSM). The median duration of observation was 451 days (IQR 357-488), totaling 5132 py.Four HIV infections were diagnosed, incidence rate 0,078/100py (95% CI 0.029-0.208). For two suboptimal adherence was reported and in the third case suboptimal adherence and resistance to emtricitabine was observed. One infection was likely acquired before PrEP start.Incidence rates were 21.6/100py for chlamydia, 23.7/100py for gonorrhea, 10.1/100py for syphilis and 55.4/100py for any STI and decreased significantly during the observation period. 65.5% of syphilis, 55.6% of chlamydia and 50.1% of gonorrhea cases were detected by screening of asymptomatic individuals. In a multivariable analysis among MSM younger age, PrEP start before health insurance coverage and daily PrEP were associated with greater risk for chlamydia/gonorrhea. Symptom triggered testing and a history of STI were associated with a higher risk for chlamydia/gonorrhea and syphilis. A significantly lower risk for chlamydia/gonorrhea and syphilis was found for observations during the covid-19 pandemic period.ConclusionsWe found that HIV-PrEP is almost exclusively used by MSM in Germany. A very low incidence of HIV-infection and decreasing incidence rates of STIs were found in this cohort of PrEP users. The results were influenced by the SARS-CoV-2 pandemic. Rollout of PrEP covered by health insurance should be continued to prevent HIV infections. Increased PrEP availability to people at risk of HIV infection through the elimination of barriers requires further attention. Investigation and monitoring with a longer follow-up would be of value.

Objectives of this study, as part of a nation-wide HIV pre-exposure prophylaxis (PrEP) evaluation project, were to determine the incidence of infections with HIV, chlamydia, gonorrhea, syphilis, hepatitis A/B/C in persons using PrEP, and to describe the health care funded PrEP use in Germany. Additionally, factors associated with chlamydia/gonorrhea and syphilis infections were assessed.Anonymous data of PrEP users were collected at 47 HIV-specialty centers from 09/2019-12/2020. Incidence rates were calculated per 100 person years (py). Using longitudinal mixed models, we analyzed risk factors associated with sexually transmitted infections (STIs).4620 PrEP users were included: 99.2% male, median age 38 years (IQR 32-45), 98.6% men who have sex with men (MSM). The median duration of PrEP exposure was 451 days (IQR 357-488), totaling 5132 py. Four HIV infections were diagnosed, incidence rate 0,078/100py (95% CI 0.029-0.208). For two, suboptimal adherence was reported and in the third case, suboptimal adherence and resistance to emtricitabine were observed. One infection was likely acquired before PrEP start. Incidence rates were 21.6/100py for chlamydia, 23.7/100py for gonorrhea, 10.1/100py for syphilis and 55.4/100py for any STI and decreased significantly during the observation period. 65.5% of syphilis, 55.6% of chlamydia and 50.1% of gonorrhea cases were detected by screening of asymptomatic individuals. In a multivariable analysis among MSM younger age, PrEP start before health insurance coverage and daily PrEP were associated with greater risk for chlamydia/gonorrhea. Symptom triggered testing and a history of STI were associated with a higher risk for chlamydia/gonorrhea and syphilis. A significantly lower risk for chlamydia/gonorrhea and syphilis was found for observations during the COVID-19 pandemic period.We found that HIV-PrEP is almost exclusively used by MSM in Germany. A very low incidence of HIV infection and decreasing incidence rates of STIs were found in this cohort of PrEP users. The results were influenced by the SARS-CoV-2 pandemic. Rollout of PrEP covered by health insurance should be continued to prevent HIV infections. Increased PrEP availability to people at risk of HIV infection through the elimination of barriers requires further attention. Investigation and monitoring with a longer follow-up would be of value.

This contribution addresses the impact of tempering processes on the emissivity of LowE glass. The current status of a measurement series conducted at various tempering sites on different types of LowE glass is presented. Emissivity measurements using inductive eddy current sensors have been made on glass before and after tempering. The obtained data shows an improvement by factor 2 in emissivity depending on coating type. Effects from tempering recipes and the resulting emissivity homogeneity have been analyzed. Measurements also show significant worsening of the emissivity by the use of wrong tempering settings where too little convection occurs during heating that cause glass bending leading to the well-known white marks in the center of the glass along with significant loss in emissivity. Assessment of the glass emissivity properties as well as the negative effects of poor furnace recipe optimization on coatings were measured by eddy current systems, which rely on inductive methods for contact or non-contact real-time emissivity assessment. Comparison to thermographic images are shown and discussed. Finally, the status of measurement and analysis are summarized and the potentials to use of these phenomena are discussed.

Hintergrund Die Steuerungsinstrumente der Arzneimittelversorgung in der gesetzlichen Krankenversicherung (GKV) sind schon länger Bestandteil der gesundheitspolitischen Reformdebatte. Über die Jahre hat sich eine Gemengelage sehr verschiedener Werkzeuge herausgebildet, die zumeist auf eine Kontrolle der Arzneimittelausgaben zielen. Die Instrumente der regionalen Verordnungssteuerung fokussieren vor allem auf eine Verhaltenssteuerung des verordnenden Arztes. Zu erwähnen ist nicht zuletzt der verstärkte Einsatz von indikationsbezogenen Quoten, vorrangig Leitsubstanzen und/oder Generika/Biosimilars. Diese gibt es mittlerweile auch im Bereich des Humanen Immundefizienz-Virus (HIV), etwa die seit 2020 in Bayern und Berlin eingeführten Generikaquoten für HIV-Therapeutika. Zielstellung Ziel des vorliegenden Beitrages ist es, auf Grundlage von GKV-Apothekenabrechnungsdaten das Potenzial sowie Grenzen von Generikaquotenlösungen in der HIV-Versorgung zu analysieren und Handlungsempfehlungen zu skizzieren. Ergebnisse Es zeigte sich, dass das Quotenpotenzial für Generika im patentfreien Bereich in der HIV-Versorgung bereits weitgehend ausgeschöpft wird. Dieser Umstand ist vor allem darauf zurückzuführen, dass die HIV-Verordner den Austausch durch Verzicht auf Aut-idem-Kreuze auf dem Kassenrezept unterstützen. Diskussion Das steuerungspolitische Optimum ist fast erreicht. Dies ist auf das geeignete Instrumentarium zurückzuführen, das aus dem Rahmenvertrag zur Arzneimittelversorgung und einer leitliniengerechten Wirkstoffverordnung durch den Arzt besteht – in Verbindung mit dem AMNOG(Arzneimittelmarktneuordnungsgesetz)-Verfahren und Festbeträgen. Leitlinienkonformität und (existierende) Eintablettenregime müssen beibehalten werden, damit die gute Versorgungsqualität gewährleistet bleibt., Background Instruments controlling statutory healthcare medical supply have long been a topic of debate in health policy reform discussions. Over the years, a variety of tools have been developed, most of which are aimed at controlling drug expenditure. The instruments controlling regional prescriptions primarily focus on controlling behavioural patterns of the prescribing physicians. Important to note is the increased use of indication-directed quotas, primarily of drug leads and/or generics/biosimilars. These are now also available in the area of the human immunodeficiency virus (HIV), such as the generic quotas for HIV medications introduced in Bavaria and Berlin in 2020. Objective The aim of this article is to analyse the benefits and limitations of generic quota solutions in HIV care using statutory health insurance drug prescription data and to outline recommendations for action. Results It was observed that the quota potential for generics in the area of patent-free drugs in HIV care has already been largely exhausted. This can be explained by HIV prescribers supporting product exchange on the prescription. Discussion The best-case scenario in terms of regulation has almost been reached. This is due to a suitable set of instruments, including the framework agreement for medical supply as well as prescribing according to guidelines – in conjunction with the Pharmaceuticals Market Reorganisation Act (AMNOG) and reference prices for drugs. Conforming with guidelines and (existing) single-tablet regimens play an integral role in maintaining good quality of care.

We exploit detailed transaction and position data for a sample of long-short equity hedge funds to study the trading activity of fundamental investors. We find that hedge funds exhibit skill in opening positions, but that they close their positions too early, thereby forgoing about one-third of the trades’ potential profitability. We explain this behavior with the limits of arbitrage: hedge funds close positions early in order to reallocate their capital to more profitable investments and/or to accommodate tightened financial constraints. Consistent with this view, we document that hedge funds leave more money on the table after opening new positions, negative returns, or increases in funding constraints and volatility. (JEL G11, G12, G14, G15)

In Rebooting Capitalism: How We Can Forge a Society that Works for Everyone, Anthony Biglan (2020) explains that a free-market and capitalist narrative, sculpted by a coalition of the extremely wealthy, has led to a commonly held myth that the pursuit of individual wealth will improve the overall well-being of the populous. Instead, our current economic system and public policies have resulted in cultural practices that increase wealth inequality, incite racial tensions, and destroy the natural world. The book functions as a call to arms for behavior analysts to join a coalition of interdisciplinary professionals with a like-minded mission of creating a nurturing form of capitalism, grounded in behavior science, that improves the quality of life for all people.

Biochemistry 60(8), 621 - 634 (2021). doi:10.1021/acs.biochem.0c00910, Chlorite dismutases (Clds) are heme b-containing oxidoreductases that can decompose chlorite to chloride and molecular oxygen. They are divided in two clades that differ in oligomerization, subunit architecture, and the hydrogen-bonding network of the distal catalytic arginine, which is proposed to switch between two conformations during turnover. To understand the impact of the conformational dynamics of this basic amino acid on heme coordination, structure, and catalysis, Cld from Cyanothece sp. PCC7425 was used as a model enzyme. As typical for a clade 2 Cld, its distal arginine 127 is hydrogen-bonded to glutamine 74. The latter has been exchanged with either glutamate (Q74E) to arrest R127 in a salt bridge or valine (Q74V) that mirrors the setting in clade 1 Clds. We present the X-ray crystal structures of Q74V and Q74E and demonstrate the pH-induced changes in the environment and coordination of the heme iron by ultraviolet���visible, circular dichroism, and electron paramagnetic resonance spectroscopies as well as differential scanning calorimetry. The conformational dynamics of R127 is shown to have a significant role in heme coordination during the alkaline transition and in the thermal stability of the heme cavity, whereas its impact on the catalytic efficiency of chlorite degradation is relatively small. The findings are discussed with respect to (i) the flexible loop connecting the N-terminal and C-terminal ferredoxin-like domains, which differs in clade 1 and clade 2 Clds and carries Q74 in clade 2 proteins, and (ii) the proposed role(s) of the arginine in catalysis., Published by American Chemical Society, Columbus, Ohio

We report the synthesis and structure/property correlations of a series of eight poly(ionic liquid)s (PILs) obtained from sequential AA + BB polyaddition by copper(I)-catalyzed azide–alkyne cycloaddition and the subsequent N-alkylation reaction. The different repeat units contain one to four ion pairs, with one to four bis(trifluorosulfonyl)imide (TFSI) anions and one or two types of ammonium, imidazolium or 1,2,3-triazolium counter-cations. Their physical, ion conducting and electrochemical properties are discussed based on the repeat unit charge density and structure of the cationic moieties. The comparison of several pairs of polyelectrolytes revealed that ionic conductivity is dependent on (1) the ratio between the number of charge carriers per monomer unit and the number of surrounding atoms/groups that can solvate the ions and (2) the nature of the cation. The highest conductivity (1.8 × 10−5 S cm−1 at 25 °C) was reached when PILs contain two 1,2,3-triazolium cations that are separated by an oxyethylene spacer. The incorporation of an additional type of cation (either imidazolium or ammonium with 1,2,3-triazolium) in one PIL allows its cathodic limit to be increased up to −0.4 V vs. Li+/Li (70 °C) and the oxidation instability of 1,2,3-triazolium cations to be overcome.

A thermally cured epoxy/anhydride system is shown to exhibit dose-dependent increases in cross-link density, glass transition temperature, and modulus. The addition of various sensitizers further b...