A role for TGFβ signalling in medium spiny neuron differentiation of human pluripotent stem cells

Activin A and other TGFβ family members have been shown to exhibit a certain degree of promiscuity between their family of receptors. We previously developed an efficient differentiation protocol using Activin A to obtain medium spiny neurons (MSNs) from human pluripotent stem cells (hPSCs). However, the mechanism underlying Activin A-induced MSN fate specification remains largely unknown. Here we begin to tease apart the different components of TGFβ pathways involved in MSN differentiation and demonstrate that Activin A acts exclusively via ALK4/5 receptors to induce MSN progenitor fate during differentiation. Moreover, we show that Alantolactone, an indirect activator of Smad2/3 signalling, offers an alternative approach to differentiate hPSC-derived forebrain progenitors into MSNs. Further fine tuning of TGFβ pathway by inhibiting BMP signalling with LDN193189 achieves accelerated MSN fate specification. This study therefore establishes an essential role for TGFβ signalling in human MSN differentiation and provides a fully defined and highly adaptable small molecule-based protocol to obtain MSNs from hPSCs

Grammatical roles, Coherence Relations, and the interpretation of pronouns in Chinese

This paper reports on an experimental study of the interpretation of pronouns in Chinese which provides additional support for the proposal in Yang et al. (1999, 2003) that the resolution of pronominal reference in Chinese is more influenced by syntactic information than often assumed in approaches to discourse anaphora in Chinese such as Li and Thompson (1979), Givon (1983), Chen (1986), Christensen (2000), and Pu (2011), where the interpretation of such elements is solely attributed to semantic, pragmatic, and discourse structure-related factors. The paper makes use of a series of sentence completion tasks, adapted from Kehler and Rohde (2013) for Chinese, to try to tease apart the often complex roles played by syntactic position, Coherence Relations, and discourse structure

Digital Affordances and Digital Capabilities: Evidence from Six AI Startups

Many digital startups fail in their pursuit of niche business value for three reasons: underdeveloped digital affordances, inadequate digital capabilities, and perhaps most importantly, a misalignment between digital affordances and digital capabilities. Digital affordances depict the potential involvement of digital technologies by groups in value creation while digital capabilities represent the ability to leverage and make changes to digital resources to fulfil specific objectives (e.g., affordance actualization). Based on insights derived from a longitudinal in-depth case study of six AI startups, we propose a co-evolution framework that illustrates several iterative loops between digital capabilities and digital affordances. Our analysis also reveals key properties of digital affordances and digital capabilities. Specifically, we find that digital startups with mutually reinforcing digital affordances and digital capabilities are most likely to succeed. We also develop a typology of digital startups using a 2 by 2 affordance-capability matrix

Contour Integration over Time: Psychophysical and fMRI Evidence.

The brain integrates discrete but collinear stimuli to perceive global contours. Previous contour integration (CI) studies mainly focus on integration over space, and CI is attributed to either V1 long-range connections or contour processing in high-visual areas that top-down modulate V1 responses. Here, we show that CI also occurs over time in a design that minimizes the roles of V1 long-range interactions. We use tilted contours embedded in random orientation noise and moving horizontally behind a fixed vertical slit. Individual contour elements traveling up/down within the slit would be encoded over time by parallel, rather than aligned, V1 neurons. However, we find robust contour detection even when the slit permits only one viewable contour element. Similar to CI over space, CI over time also obeys the rule of collinearity. fMRI evidence shows that while CI over space engages visual areas as early as V1, CI over time mainly engages higher dorsal and ventral visual areas involved in shape processing, as well as posterior parietal regions involved in visual memory that can represent the orientation of temporally integrated contours. These results suggest at least partially dissociable mechanisms for implementing the Gestalt rule of continuity in CI over space and time

Converting capsules to sensors for nondestructive analysis:from cargo-responsive self-sensing to functional characterization

A general concept of converting capsules into sensors is reported. Such simple conversion enables instantaneous nondestructive analysis for applications such as controlled release and energy storage among others. Converted capsule sensors are responsive in emission colors to varying core cargos via the incorporation of a solvatochromic fluorophore under excitation. Such cargo-responsive self-sensing abilities facilitate their application in capsule-level analysis such as cargo retention-leakage detection and release implications, as well as defect identification. The versatile concept is shown as an auxiliary tool in thermal energy storage to visualize phase transition, exhibiting promising potentials in application-level characterization

Spectral properties of the exponential distance matrix

Given a graph $G$, the exponential distance matrix is defined entry-wise by letting the $(u,v)$-entry be $q^{\text{dist}(u,v)}$, where $\text{dist}(u,v)$ is the distance between the vertices $u$ and $v$ with the convention that if vertices are in different components, then $q^{\text{dist}(u,v)}=0$. In this paper, we will establish several properties of the characteristic polynomial (spectrum) for this matrix, give some families of graphs which are uniquely determined by their spectrum, and produce cospectral constructions

The reliability of immunoassays to detect autoantibodies in patients with myositis is dependent on autoantibody specificity

OBJECTIVES: In order to address the reliability of commercial assays to identify myositis-specific and -associated autoantibodies, we aimed to compare the results of two commercial immunoassays with the results obtained by protein immunoprecipitation.METHODS: Autoantibody status was determined using radio-labelled protein immunoprecipitation for patients referred to our laboratory for myositis autoantibody characterization. For each autoantibody of interest, the sera from 25 different patients were analysed by line blot (Euroline Myositis Antigen Profile 4, EuroImmun, Lübeck, Germany) and dot blot (D-Tek BlueDiver, Diagnostic Technology, Belrose, NSW, Australia). Sera from 134 adult healthy controls were analysed.RESULTS: Overall commercial assays performed reasonably well, with high agreement (Cohen's κ &gt;0.8). Notable exceptions were the detection of rarer anti-synthetases with κ &lt; 0.2 and detection of anti-TIF1γ, where κ was 0.70 for the line blot and 0.31 for dot blot. Further analysis suggested that the proportion of patients with anti-TIF1γ may recognize a conformational epitope, limiting the ability of blotting-based assays that utilize denatured antigen to detect this clinically important autoantibody. A false-positive result occurred in 13.7% of samples analysed by line blot and 12.1% analysed by dot blot.CONCLUSION: The assays analysed do not perform well for all myositis-specific and -associated autoantibodies and overall false positives are relatively common. It is crucial that clinicians are aware of the limitations of the methods used by their local laboratory. Results must be interpreted within the clinical context and immunoprecipitation should still be considered in selected cases, such as apparently autoantibody-negative patients where anti-synthetase syndrome is suspected.</p

The feasibility and challenges of energy self-sufficient wastewater treatment plants

Energy efficiency optimization is crucial for wastewater treatment plants (WWTPs) because of increasing energy costs and concerns about global climate change. Energy efficiency optimization can be achieved through a combination of energy recovery from the wastewater treatment process and energy saving-related technologies. Through these two approaches energy self-sufficiency of WWTPs is achievable, and research is underway to reduce operation costs and energy consumption and to achieve carbon neutrality. In this paper, we analyze energy consumption and recovery in WWTPs and characterize the factors that influence energy use in WWTPs, including treatment techniques, treatment capacities, and regional differences. Recent advances in the optimization of energy recovery technologies and theoretical analysis models for the analysis of different technological solutions are presented. Despite some challenges in implementation, such as technological barriers and high investment costs, particularly in developing countries, this paper highlights the potential for more energy self-sufficient WWTPs to be established in the future