Novel tissue markers in renal neoplasms using molar-scale quantitative proteomics via the total protein approach normalised with protein deglycase DJ-1 (PARK7)

Mass spectrometry-based proteomics enables large-scale protein quantification but is hindered by inter- and intra-laboratory variability, complicating data integration and biomarker discovery. This study aims to develop an optimised normalisation strategy using the ubiquitously expressed protein deglycase DJ-1 (PARK7) as an internal standard, combined with the Total Protein Approach (TPA) to improve data comparability in renal neoplasms proteomic datasets. We analysed the MS-based proteomics data of renal tissues from clear cell renal cell carcinoma (ccRCC, n = 7), papillary renal cell carcinoma (pRCC, n = 5), chromophobe renal cell carcinoma (chRCC, n = 5), renal oncocytoma (RO, n = 5), and control normal adjacent tissue (NAT, n = 5). Protein concentrations were calculated using the Total Protein Approach, and the data were normalised to PARK7 expression using a TPA reference value of 34.1 pmol/mg. TPA-PARK7 normalisation showed a trend towards reducing interquartile ranges. After normalisation, 95 % of biomarkers from non-normalised datasets remained statistically significant. Among these, 31 % of previously proposed candidate biomarkers retained their ability to distinguish between conditions, with histologically validated biomarkers (TUBB3, LAMP1, and HK1) showing improved differentiation. Additionally, 322 new statistically significant proteins were identified, and 18 new potential biomarkers for renal neoplasm were detected exclusively after TPA-PARK7 normalisation. Our findings demonstrate that using PARK7 as an internal standard, combined with the TPA, significantly enhances the statistical robustness and reliability of protein quantification in mass spectrometry-based proteomics. This normalisation strategy reduces interlaboratory variability, preserves biomarker differentiation capability, and enables novel biomarker discovery. By reducing variability, this method enhances cross-study comparability and supports the advancement of clinically relevant biomarker discovery

A comprehensive approach to incorporating intermolecular dispersion into the openCOSMO-RS model. Part 2: Atomic polarizabilities

OpenCOSMO-RS is an open-source predictive thermodynamic model that can be applied to a broad range of systems in various chemical and biochemical engineering domains. This study focuses on improving openCOSMO-RS by introducing a new dispersion term based on atomic polarizabilities. We evaluate different methods for processing polarizability data, including scaling and combining it to compute segment-segment dispersion interaction energies, with a focus on halocarbon systems. The results demonstrate that the modified model outperforms our previous method developed in the first part of this work Grigorash et al. (2024), while at the same time requiring fewer adjustable parameters. The approach was applied to a broad dataset of over 50,000 data points, consistently increasing the accuracy across a variety of data types. These findings suggest that atomic polarizability is a valuable descriptor for refining dispersion interactions in predictive thermodynamic models

Energetic perspective on the crystal structure organization principles of meta-halogen-substituted anilines

The crystal structures of meta-halogenated anilines 3-chloro- and 3-bromaniline have been determined for the first time. The crystal structure 3-iodoanoiline was re-determined with a sufficient quality using single-crystal X-ray diffraction. All three structures were analyzed from both geometric and energetic perspectives. Geometric analysis reveals common motifs such as zig-zag chains, bifurcated halogen bonds, and the dual donor–acceptor role of amino groups in hydrogen bonding. An energy-based approach, utilizing quantum chemical calculations, enables identification of the dominant interactions and basic structural motifs. While 3-chloroaniline forms columnar structures dominated by N–H···N and C–H···π interactions, the bromo- and iodo-analogs exhibit isostructural columnar-layered packing motives governed by stronger halogen bonding and π-type interactions. This combined approach emphasizes the importance of energy analysis in distinguishing structural hierarchies in systems with multiple weak interactions

Taxing people

The modern international tax system is a complex framework of national laws, bilateral treaties, and multilateral agreements aimed at coordinating state tax entitlements. Historically, taxation was based on political allegiance, but globalization and increased mobility introduces new challenges. As more people and businesses operate across borders, it becomes harder to determine which states have the right to tax them. Fragmentation of individuals' economic and political lives has complicated states' abilities to balance liberty, justice, and collective decision-making. Taxing People addresses taxes on individuals, which are crucial for providing public goods, promoting justice, and legitimizing state power. Exploring the future of individual taxation, the book focuses on global tax governance, social changes like remote work, and the evolving relationship between people and states in a globalized economy

Spatial and social cognition jointly determine multimodal demonstrative reference: Experimental evidence from Turkish and Spanish

All languages in the world have demonstrative terms such as ‘this’ and ‘that’ in English, which have traditionally been treated as spatial words. Here we aim to provide experimental evidence that demonstrative choice is jointly determined by spatial considerations (e.g., whether the referent is near or far) and socio-cognitive factors (e.g.,the listener’s attention focus). We also test whether demonstrative choice varies depending on the speaker’s use of pointing, to provide evidence for a multimodal account of demonstrative systems. We focus on the Turkish system and compare it with the Spanish one to better understand the cross-linguistic variability of 3-term demonstrative systems. Corpus studies have suggested that the Turkish proximal ‘bu’ and distal ‘o’ mark a spatial contrast between near and far space, whereas the medial ‘s¸u’ is used to direct the listener’s attention to a new referent. Supporting this analysis, an online experiment using a picture-based demonstrative-choice task revealed that the medial form ‘s¸u’ was preferred when the listener was looking at the wrong object. The results of a second experiment using video stimuli further showed that the medial ‘s¸u’ was preferred when the speaker pointed to the referent to direct the listener’s attention, whereas the proximal demonstrative was used in near space and the distal in far space, mostly in joint attention and without pointing. The results of a third experiment in Spanish showed radically different patterns of demonstrative-pointing use. The medial ‘ese’ was preferred in joint attention, whereas the proximal ‘este’ and distal ‘aquel’ were selected to direct the listener’s attention towards the intended referent but without an effect of pointing. Our results confirm that demonstrative choice within a given system is determined by both spatial and socio-cognitive factors, interacting with pointing patterns and varying across languages. Leveraging recent experimental work in several languages, we interpret these findings as further evidence for the weighted parameters framework (e.g., referent position and listener attention), which explains demonstrative choice beyond previous categorical analyses