The MacLane class and the Eremenko-Lyubich class

In 1970 G. R. MacLane asked if it is possible for a locally univalent function in the class A to have an arc tract. This question remains open, but several results about it have been given. We significantly strengthen these results, in particular replacing the condition of local univalence by the more general condition that the set of critical values is bounded. Also, we adapt a recent powerful technique of C. J. Bishop in order to show that there is a function in the Eremenko-Lyubich class for the disc that is not in the class A

Steric Exclusion Chromatography for Purification of Biomolecules—A Review

Steric exclusion chromatography (SXC) is a purification method that is based on steric exclusion effects from the surface of the target and a hydrophilic stationary phase after the addition of polyethylene glycol (PEG), which leads to an association of the target with the stationary phase without direct binding, such as covalent, electrostatic, and hydrophilic/hydrophobic interactions. The gentle nature of the method has led to an increased focus on sensitive targets such as enveloped viruses with potential for other sensitive entities, e.g., extracellular vesicles and virus-like particles. SXC is related to PEG-mediated protein precipitation, but investigation of further process parameters was crucial to gain a better understanding of the SXC method. After explaining mechanistic fundamentals and their discovery, this review summarizes the findings on SXC from its first reference 11 years ago until today. Different applications of SXC are presented, demonstrating that the method can be used for a wide variety of targets and achieves high recovery rates and impurity removal. Further, critical process parameters for successful process implementation are discussed, including technical requirements, buffer composition, and scalability

Infectious titer determination of lentiviral vectors using a temporal immunological real-time imaging approach

The analysis of the infectious titer of the lentiviral vector samples obtained during upstream and downstream processing is of major importance, however, also the most challenging method to be performed. Currently established methods like flow cytometry or qPCR lack the capability of enabling high throughput sample processing while they require a lot of manual handling. To address this limitation, we developed an immunological real-time imaging method to quantify the infectious titer of anti-CD19 CAR lentiviral vectors with a temporal readout using the Incucyte® S3 live-cell analysis system. The infective titers determined with the Incucyte® approach when compared with the flow cytometry-based assay had a lower standard deviation between replicates and a broader linear range. A major advantage of the method is the ability to obtain titer results in real-time, enabling an optimal readout time. The presented protocol significantly decreased labor and increased throughput. The ability of the assay to process high numbers of lentiviral samples in a high throughput manner was proven by performing a virus stability study, demonstrating the effects of temperature, salt, and shear stress on LV infectivity

The Exozodiacal Dust Problem for Direct Observations of ExoEarths

Debris dust in the habitable zones of stars - otherwise known as exozodiacal dust - comes from extrasolar asteroids and comets and is thus an expected part of a planetary system. Background flux from the Solar System's zodiacal dust and the exozodiacal dust in the target system is likely to be the largest source of astrophysical noise in direct observations of terrestrial planets in the habitable zones of nearby stars. Furthermore, dust structures like clumps, thought to be produced by dynamical interactions with exoplanets, are a possible source of confusion. In this paper, we qualitatively assess the primary impact of exozodical dust on high-contrast direct imaging at optical wavelengths, such as would be performed with a coronagraph. Then we present the sensitivity of previous, current, and near-term facilities to thermal emission from debris dust at all distances from nearby solar-type stars, as well as our current knowledge of dust levels from recent surveys. Finally, we address the other method of detecting debris dust, through high-contrast imaging in scattered light. This method is currently far less sensitive than thermal emission observations, but provides high spatial resolution for studying dust structures. This paper represents the first report of NASA's Exoplanet Exploration Program Analysis Group (ExoPAG).Comment: 21 pages, 5 figures, 2 tables. Accepted for publication in PASP 2012-06-0

Effects of short-chain fatty acids on intestinal function in an enteroid model of hypoxia

The healthy GI tract is physiologically hypoxic, but this may be perturbed by certain acute and chronic stressors that reduce oxygen availability systemically. Short-chain fatty acids have been shown to have beneficial effects on intestinal barrier function and inflammation. Therefore, our objective was to see whether short-chain fatty acids (SCFA) would improve GI barrier function, reduce production of pro-inflammatory cytokines, and increase the expression of genes regulating GI barrier function in enteroids exposed to hypoxia. Human duodenal enteroid monolayers were placed under hypoxia (1.0% O2) for 72 h with either 24, or 48 h pre-treatment with a high acetate ratio of SCFA’s or high butyrate ratio or placed under hypoxia concurrently. Transepithelial electrical resistance (TEER) increased with SCFA pre-treatment, especially 48 h of pre-treatment and this was maintained through the first 48 h of hypoxia while cells saw barrier function dramatically decrease by 72 h of hypoxia exposure. Inflammatory protein secretion largely decreased with exposure to hypoxia, regardless of SCFA pre-treatment. Gene expression of several genes related to barrier function were decreased with exposure to hypoxia, and with concurrent and 24 h SCFA pre-treatment. However, 48 h SCFA pre-treatment with a high butyrate ratio increased expression of several metabolic and differentiation related genes. Overall, pre-treatment or concurrent treatment with SCFA mixtures were not able to overcome the negative impacts of hypoxia on intestinal function and cells ultimately still cannot be sustained under hypoxia for 72 h. However, 48 h pre-treatment maintains TEER for up to 48 h of hypoxia while upregulating several metabolic genes

Salen Mn Complexes Mitigate Radiation Injury in Normal Tissues

Salen Mn complexes, including EUK-134, EUK-189 and a newer cyclized analog EUK-207, are synthetic SOD/catalase mimetics that have beneficial effects in many models of oxidative stress. As oxidative stress is implicated in some forms of delayed radiation injury, we are investigating whether these compounds can mitigate injury to normal tissues caused by ionizing radiation. This review describes some of this research, focusing on several tissues of therapeutic interest, namely kidney, lung, skin, and oral mucosa. These studies have demonstrated suppression of delayed radiation injury in animals treated with EUK-189 and/or EUK-207. While an antioxidant mechanism of action is postulated, it is likely that the mechanisms of radiation mitigation by these compounds in vivo are complex and may differ in the various target tissues. Indicators of oxidative stress are increased in lung and skin radiation injury models, and suppressed by salen Mn complexes. The role of oxidative stress in the renal injury model is unclear, though EUK-207 does mitigate. In certain experimental models, salen Mn complexes have shown “mito-protective” properties, that is, attenuating mitochondrial injury. Consistent with this, EUK-134 suppresses effects of ionizing radiation on mitochondrial function in rat astrocyte cultures. In summary, salen Mn complexes could be useful to mitigate delayed radiation injury to normal tissues following radiation therapy, accidental exposure, or radiological terrorism. Optimization of their mode of delivery and other key pharmaceutical properties, and increasing understanding of their mechanism(s) of action as radiation mitigators, are key issues for future study

Target Selection for the LBTI Exozodi Key Science Program

The Hunt for Observable Signatures of Terrestrial planetary Systems (HOSTS) on the Large Binocular Telescope Interferometer will survey nearby stars for faint emission arising from ~300 K dust (exozodiacal dust), and aims to determine the exozodiacal dust luminosity function. HOSTS results will enable planning for future space telescopes aimed at direct spectroscopy of habitable zone terrestrial planets, as well as greater understanding of the evolution of exozodiacal disks and planetary systems. We lay out here the considerations that lead to the final HOSTS target list. Our target selection strategy maximizes the ability of the survey to constrain the exozodi luminosity function by selecting a combination of stars selected for suitability as targets of future missions and as sensitive exozodi probes. With a survey of approximately 50 stars, we show that HOSTS can enable an understanding of the statistical distribution of warm dust around various types of stars and is robust to the effects of varying levels of survey sensitivity induced by weather conditions.Comment: accepted to ApJ

Hierarchical Processing of Auditory Objects in Humans

This work examines the computational architecture used by the brain during the analysis of the spectral envelope of sounds, an important acoustic feature for defining auditory objects. Dynamic causal modelling and Bayesian model selection were used to evaluate a family of 16 network models explaining functional magnetic resonance imaging responses in the right temporal lobe during spectral envelope analysis. The models encode different hypotheses about the effective connectivity between Heschl's Gyrus (HG), containing the primary auditory cortex, planum temporale (PT), and superior temporal sulcus (STS), and the modulation of that coupling during spectral envelope analysis. In particular, we aimed to determine whether information processing during spectral envelope analysis takes place in a serial or parallel fashion. The analysis provides strong support for a serial architecture with connections from HG to PT and from PT to STS and an increase of the HG to PT connection during spectral envelope analysis. The work supports a computational model of auditory object processing, based on the abstraction of spectro-temporal “templates” in the PT before further analysis of the abstracted form in anterior temporal lobe areas