'Almost' in Early and Late Modern English: Turning on the Parametric Screw (But Not Tightly Enough to Change a Parameter)

This contribution investigates the decompositional behavior of ‘almost’ in Early and Late Modern English (EModE/LModE), i.e.: whether the adverb is able to modify result states of predicates to which it attaches, in addition to the default possibility of modifying the meaning of the entire events. ‘Almost’ is found to be decompositional in EModE at a time when ‘again’ was not truly so (Beck & Gergel, 2015; Gergel & Beck, 2015). This supports the view that decompositionality is primarily a lexical property. The trajectory of the decompositional behavior in EModE and LModE is, however, complicated by a series of factors, and some possible tendencies towards its decline are observed

Quantum-Mechanical Methods for Quantifying Incorporation of Contaminants in Proximal Minerals

Incorporation reactions play an important role in dictating immobilization and release pathways for chemical species in low-temperature geologic environments. Quantum-mechanical investigations of incorporation seek to characterize the stability and geometry of incorporated structures, as well as the thermodynamics and kinetics of the reactions themselves. For a thermodynamic treatment of incorporation reactions, a source of the incorporated ion and a sink for the released ion is necessary. These sources/sinks in a real geochemical system can be solids, but more commonly, they are charged aqueous species. In this contribution, we review the current methods for ab initio calculations of incorporation reactions, many of which do not consider incorporation from aqueous species. We detail a recently-developed approach for the calculation of incorporation reactions and expand on the part that is modeling the interaction of periodic solids with aqueous source and sink phases and present new research using this approach. To model these interactions, a systematic series of calculations must be done to transform periodic solid source and sink phases to aqueous-phase clusters. Examples of this process are provided for three case studies: (1) neptunyl incorporation into studtite and boltwoodite: for the layered boltwoodite, the incorporation energies are smaller (more favorable) for reactions using environmentally relevant source and sink phases (i.e., ΔErxn(oxides) > ΔErxn(silicates) > ΔErxn(aqueous)). Estimates of the solid-solution behavior of Np5+/P5+- and U6+/Si4+-boltwoodite and Np5+/Ca2+- and U6+/K+-boltwoodite solid solutions are used to predict the limit of Np-incorporation into boltwoodite (172 and 768 ppm at 300 °C, respectively); (2) uranyl and neptunyl incorporation into carbonates and sulfates: for both carbonates and sulfates, it was found that actinyl incorporation into a defect site is more favorable than incorporation into defect-free periodic structures. In addition, actinyl incorporation into carbonates with aragonite structure is more favorable than into carbonates with calcite structure; and (3) uranium incorporation into magnetite: within the configurations tested that preserve charge neutrality (U6+ → 2Fe3+oct/tet or U4+ → Fe2+oct), uranium incorporation into magnetite is most favorable when U6+ replaces octahedral Fe3+ with charge balancing accomplished by an octahedral Fe3+ iron vacancy. At the end of this article, the limitations of this method and important sources of error inherent in these calculations (e.g., hydration energies) are discussed. Overall, this method and examples may serve as a guide for future studies of incorporation in a variety of contexts

Rituximab efficiently depletes increased CD20-expressing T cells in multiple sclerosis patients.

In multiple sclerosis (MS), B cell-depleting therapy using monoclonal anti-CD20 Abs, including rituximab (RTX) and ocrelizumab, effectively reduces disease activity. Based on indirect evidence, it is generally believed that elimination of the Ag-presenting capabilities and Ag nonspecific immune functions of B cells underlie the therapeutic efficacy. However, a small subset of T lymphocytes (T cells) was shown to also express CD20, but controversy prevails surrounding the true existence of this T cell subpopulation. Using single-cell imaging flow cytometry and expression profiling of sorted lymphocyte subsets, we unequivocally demonstrate the existence of CD3(+)CD20(dim) T cells. We show that in MS patients, increased levels of CD3(+)CD20(dim) T cells are effectively depleted by RTX. The pathological relevance of this T cell subset in MS remains to be determined. However, given their potential proinflammatory functionality, depletion of CD20-expressing T cells may also contribute to the therapeutic effect of RTX and other mAbs targeting CD20

Rituximab Efficiently Depletes Increased CD20-Expressing T Cells in Multiple Sclerosis Patients

In multiple sclerosis (MS()) B cell depleting therapy using monoclonal anti-CD20 antibodies, including rituximab (RTX) and ocrelizumab (OCR), effectively reduces disease activity. Based on indirect evidence, it is generally believed that elimination of the antigen presenting capabilities and antigen non-specific immune functions of B cells underlie the therapeutic efficacy. However, a small subset of T lymphocytes (T cells) was shown to also express CD20, but controversy prevails surrounding the true existence of this T cell subpopulation. Using single-cell imaging flow cytometry and expression profiling of sorted lymphocyte subsets, we unequivocally demonstrate the existence of CD3(+)CD20(dim) T cells. We show that in MS patients increased levels of CD3(+)CD20dim T cells are effectively depleted by RTX. The pathological relevance of this T cell subset in MS remains to be determined. However, given their potential pro-inflammatory functionality, depletion of CD20-expressing T cells may also contribute to the therapeutic effect of RTX and other monoclonal antibodies targeting CD20